Investigate the emotional status and social support of methadone maintenance treatment (MMT) patients to provide guidance for a pertinent intervention.

We conducted a case-control study between 86 patients of Shanghai Changning community based methadone maintenance treatment and 93 controls from Shanghai Changning district. They were investigated via questionnaires, including Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and Social Support Scale.

The SDS scores were significantly higher in MMT group than in control group (52.7±11.4 vs 39.9±6.4, P< 0.01); the total scores of social support and subjective support, objective support and the 3 factors of support utilization were lower in MMT group compared with control group ([17.9±6.5 vs 20.3±7.8], [5.2±1.7 vs 7.4±1.4], P< 0.05); the scores of problem solving and recourse factors were lower in MMT group than in control group ([0.74±0.18 vs 0.91±0.06], [0.64±0.20 vs 0.69±0.06], P< 0.05).

The depression symptoms are prevalent in patients. The social support is low and the problem solving and recourse approaches are less utilized in patients. Our results show that it is necessary to implement the integrative intervention of MMT patients for improving the full recovery of their social function.

Nicotine dependence is a world health problem. The objective of this paper is to present the implementation of a treatment program and the use of varenicline as a specific medication for nicotine dependence during internment at our clinic in Rio de Janeiro.

The program starts with a first evaluation done by a psychiatrist. The initial dose of varenicline is 0,5 mg on the first 3 days raising to 0,5 mg twice a day from day 4 to day 7; after that it is increased to 1mg twice a day until 12 weeks are completed. It is suggested that the patient picks up a day to quit smoking, between the first and second week of use. It was also given behavioral and focal group therapy. During 14 months, we established a continuous reduction on the number of cigarettes, from 20 to 1 and finally 4 a day.

There were 354 patients attending the program from June 2008 to August 2009 and 69 (19,5%) accepted the whole program. From them, 56 (81,2%) used varenicline and all of them reached abstinence. Also, we followed these 56 patients for the last 6 months and 38 (67,8%) were still abstinent.

There was a high number of acceptance as well as of abstinence. Group and behavioral therapies can be important allies to varenicline. It is important to remember that the high cost of this medication remains an impediment for wide use. A planned reduction with cultural changes can also be very effective.

Socio-cultural and family context of Serbian post-conflict and transition society intensifies overall risks of alcohol (mis)use.

The main purpose of this article was to analyze the risk behavior of young people in relation to (mis)use of alcoholic beverages in Serbia. Five indicators were examined: use of alcohol by the very young, frequency of use of alcoholic beverages, the state of getting drunk, combination of alcohol and psychoactive substances and motives for use of alcoholic beverages.

The study included 3.111 participants aged between 16 and 35 years from different parts of Serbia. Collection of data was conducted in April 2007. Participants completed self-administered anonymous questionnaires (modified YOUTH RISK BEHAVIOUR SURVEY) that consisted of sociodemographic characteristics and experiences related to alcohol (mis)use.

Majority of participants reported drinking alcohol at the age of fifteen or younger. Lifetime alcohol use was reported by 75% participants. Prevalence of alcohol drinking was threefold higher among males. The overall prevalence of the state of getting drunk among participants was 36%. During one month before survey 10% of participants have expirienced combination of alcohol and psychoactive substances. Key motives for use of alcoholic beverages were relaxation (33%) and friendship (17%).

Early alcohol use, history of family disorganization and parental alcoholism were identified as factors related to increased risk of (mis)use of alcohol among young in Serbia.

(Mis)use of alcohol was related to significantly higher risk of other risk behaviors as marijuana use, violence, gambling, driving car in alcoholic state.

Dopaminergic pathways are implicated in motivational aspects of substance use disorders, and might contribute to withdrawal phenomena, as well as an increased long-term risk of relapse. Molecular imaging with positron emission tomography (PET) revealed reductions in the availability of binding sites for D2/3receptor ligands in striatum of withdrawn abusers of cocaine; corresponding results in alcoholics have been inconsistent so far. In the present study, we used the D2/3ligand [18F]fallypride to investigate dynamic changes in receptor availability in the striatum of patients with alcohol use disorder before and after undergoing a detoxification protocol.

18 male patients (mean age 44±5.3y) with alcohol use disorder were recruited and scanned with 180MBq [18F]fallypride upon hospital admission, and again 1-2 weeks later after detoxification. The control group consisted of 10 age-matched healthy volunteers. PET acquisition time was 180min, consisting of 39 frames of increasing duration. Within each group binding potentials (BPND) were calculated in the striatum using the cerebellum as reference.

In the patients, the mean BPND in whole striatum was 17.2±4.2 at baseline, with a trend towards a decline at follow-up. In addition there were inverse correlations of BPNDwith age (r-0.45) and with daily alcohol consumption (r-0.2). The age-dependence of BPNDwas less pronounced in healthy controls. However, mean striatal BPNDwas only slightly lower in the patient group. No pronounced group differences were evident for extrastriatal [18F]fallypride binding.

Regressions with age suggest an accelerated loss of dopamine D2/3 receptors in the striatum of subjects with alcohol use disorder.

So far, research on cognitive functions in multiple drug abusers with a very early age of onset has been only tentative. Furthermore, outcome research for therapy or rehabilitation is urgently needed in subgroups of this heterogeneous cohort of drug abusers.

Different cognitive domains (i.e. intelligence and attentiveness) of N = 750 patients were tested in a rehabilitation hospital for multiple drug abuse and comorbid mental disorder. The test results were correlated with the prominent drug cluster of the patients over the last 10 years. Calculated were also the impact of age of onset and mental disorder on the attentional system.

Drug clustering showed different effects on attentional functions. Morphine was hardly associated with serious deficits. Cannabis showed effects in the domains of multimodal stimulus processing (i.e. divided attention) and visual attention (visual scanning) with respect to cumulative lifetime dosage and the duration of use. Cumulative use of alcohol also had a negative effect on the attentional system, particularly on frontal executive functions (i.e. flexibility and working memory). The effect of amphetamines, methamphetamines and cocaine varied depending on which other drugs were used. Comorbidity (e.g., schizophrenia or developmental disorders) also had significant effects on the test results.

Specific attentional dysfunctions can lead to diminished behaviour control and impairments in professional abilities (e.g., ability to drive or operate a machine). The results of our study are important for diagnosis and planning therapy or rehabilitation especially in younger patients.

Bipolar disorder (BPD) and alcoholism are strongly comorbid and both have significant genetic influences but no consistent genetic vulnerability has been found. We aimed to find bipolar-alcoholism vulnerability genes.

A genome-wide association study (GWAS) of 510 patients with bipolar disorder (BPD), of whom 143 met Research Diagnostic Criteria (RDC) alcoholism diagnoses, and 506 ancestrally matched supernormal controls. We genotyped 372K genetic markers on an Affymetrix 500K-array. Chi-square analysis of allelic association using PLINK, and permutation testing for gene-wise association of genes previously associated with alcoholism-related phenotypes using COMBASSOC, were performed.

No marker met genomewide significance. Gene-wise analyses of markers clustering near genes already implicated in alcoholism, but which were not associated in non-alcoholic BPD, were: Cadherin-11 (CDH11, p = 6 × 10-4), Exportin 7 (XPO7), neuromedin-U receptor 2 (NMUR2), collagen type XI-alpha 2 (COL11A2) and Semaphorin-5A (SEMA5A).

These genes replicated prior genetic reports implicating “connectivity” (adhesion, migration and neuronal signalling) genes in addictions and comorbid BPD. Connectivity genes regulate neuronal connections during development and play roles in later neuroadaptive and mnemonic processes. These processes may influence addiction vulnerability, as seen clinically in denial, cognitive impairment, and repetitive substance misuse and relapse behaviour. We propose that we have identified genes i) increasing susceptibility to alcoholism that could be unmasked or released by the presence of bipolar affective disorder; ii) and genes increasing susceptibility to affective disorder that also predispose to secondary alcoholism. We were limited by small sample size. Larger future studies are needed.

Alcoholism has a high prevalence and impacts on morbidity, mortality, life quality, and the economy. Heritability estimates of alcohol dependence are 50-61%. Putative psychological, cultural, and genetic susceptibilities to alcoholism have been identified but understanding of the genetic components is still underdeveloped.

Identify genetic vulnerabilities predisposing individuals to alcoholism and co-morbid psychiatric disorders in the largest study of its kind.

12 centres including 10 trainees are currently collecting blood and clinical samples. Nearly 1700 of 2000 cases of ICD-10/DSM-IV alcohol dependence have been collected; 500 with standardized assessments of alcohol use and comorbdity; and 2000 ancestrally-matched supernormal controls from UCL/collaborators. Genomic DNA will be isolated following standard procedures. Genotyping will be performed using the Affymetrix Gene Chip Human Mapping 1M Array to type up to 1 million single nucleotide polymorphism (SNP) and copy number variant (CNV) markers. Chi-square analysis of allelic association for the alcoholic sample versus controls will occur.

n=65; 57% male; mean age 45years; mean age onset harmful alcohol use 19years; mean age onset withdrawals 32y; mean alcohol intake 21 units; primary depression 27%; secondary depression 49%; antisocial personality disorder 14%. The candidate gene approach in this sample has shown that the GABA receptor B1 (GABRB1) and the tachykinin receptor 1 (TACR1) are involved in genetic susceptibility to alcoholism. The D2 dopamine receptor is next.

Preliminary data suggests high psychiatric comorbidity in a clinical alcohol dependence sample and implicated candidate genes. Next is genomewide analysis of markers, sequencing and biological pathway/systems alterations.

The Teen Addiction Severity Index (T-ASI), the MMPI-A, and an inventory of drug use pattern were administered to 73 psychiatric patients (M=16.0, SD=1.18 years old; 51% male).

Rho Spearman correlations showed significant associations between Disconstraint (DISC) and T-ASI indexes of drug and social problems (rho= .342, p= .003, and rho= .320, p= .006) and also between DISC in relation to level of cannabis use and other drugs than cocaine and amphetamines (rho= .334, p= .004, and rho= .274, p= .023). The dimension of Psychoticism (PSYC) and Aggressiveness (AGGR) showed slight association with cannabis use (rho= .236, p= .045, and rho= .247, p= .035). The Negative emotionality (NEGE) and Introversion (INTR) showed a moderate association with the T-ASI index of psychiatric problems (rho= .265, p=0.023, and rho=.256, p= .029) but not with drug problems.

The DISC trait could represent a good indicator of risk for drug related problems. High scores in PSYC and AGGR are slightly associated to increase level of cannabis use. While psychiatric complaints are associated with NEGE and INTR traits.

Startle reflex (SR) is a defensive response to sudden, intense stimuli. Prepulse inhibition (PPI) refers to the ability of innocuous sensory events to reduce SR. PPI has been described as an operational measure of sensorimotor gating that is reduced in several neuropsychiatric disorders, such as schizophrenia, but there is no extensive experience in addictions and alcoholism. The objective of this study was to examine the existence of impairments on SR and PPI in abstinent alcoholic males.

Subjects were 40 abstinent alcoholic males, aged 18 to 65 years (mean age 44.73), who had met DSM-IV criteria for Alcohol Dependence, being abstinent for more than a month at the moment they were tested. Participants underwent testing for PPI. Subjects were then compared with 35 equal controls.

Magnitudes of the SR were lower in abstinent alcoholic males when compared with controls. This differences were significant (p< 0,05) in trials with prepulse presented 30, 60 or 120 msec before the onset of startle stimulus. There was a significant less percentage of PPI when prepulse was presented 30 msec before the startle stimulus (p< 0,05).

Abstinent alcoholic males exhibit a decrease in the startle response magnitude and in the PPI of the SR. These data suggest that sensory information processing mechanisms could be damaged in abstinent alcoholic patients. The fact that these findings are common to other psychiatric disorders, could indicate the existence of a common vulnerability marker, and could explain the important comorbidity between alcoholism and other mental illness.

Impulsivity has been considered as a risk factor for alcohol dependence. Recent research is focusing on paradigms of the startle response (SR), specifically prepulse inhibition (PPI) and startle habituation (SH), as vulnerability markers for alcoholism. It has been demonstrated impairments in the PPI and the SH in offspring of alcoholics. It has also been shown, using personality questionnaires, that faster habituation may be associated with tendency toward impulsivity and behavioral disinhibition. Our goal is to study the correlation between impulsivity laboratory measures and the SR paradigms, in order to see if they could share a common base as endophenotypes for alcoholism.

The subjects were 40 abstinent alcoholic males, aged 18 to 65 years (mean age 44.73) and who had met DSM-IV criteria for Alcohol Dependence, being abstinent for more than a month at the moment they were tested. Participants underwent testing for PPI and habituation of the acoustic startle response. Impulsivity was assessed with three different laboratory measures: Continuous Performance Test (CPT), Stop-Signal Task and Differential Reinforcement for Low-Rate Responding (DRL6). Analyses were performed using SPSS v.10.0.

We found a significant positive correlation between CPT-tasks and SH (p< 0,01), and Stop-Signal Task-tasks and SH (p< 0,05), but not with DRL6-tasks. No significant correlation was demonstrated between impulsivity measures and PPI.

Our findings suggest the existence of a common base between impulsivity and SH as vulnerability markers for alcohol dependence. Further studies are needed to assess if both could share a common genetic origin.

Topiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence. However, adverse events can limit its use in different clinical situation. In this randomised, double-blind, placebo controlled trial we aimed to investigate the efficacy of low-dosage topiramate on alcohol drinking indices. Craving and psychiatric symptoms improvements were the secondary endpoints.

Forty alcohol dependent subjects where detoxified and subsequently randomised into two groups, respectively receiving topiramate (100mg/die) or Placebo. The level of craving for alcohol was evaluated by a 10-cm Visual Analogue Scale (VAS) and the Italian -version of the Obsessive and Compulsive Drinking Scale (OCDS). Psychiatric symptomatology was evaluated by the Symptom Check List 90 Revised (SCL-90 R).

The improvement of alcohol drinking indices and craving scores was higher in the topiramate group than placebo. The survival function showed that patients treated with topiramate remained abstinent from any alcohol amount for a longer time with respect to placebo (Z= -2.197; P< 0.05). The SCL-90-R general index of “Positive Symptom Total” significantly reduced in the topiramate group (F= 3.41, p< 0.05). The number of patients dropped-out from the study for adverse events was not different between groups.

To our knowledge, this is the first randomised, parallel group trial to evaluate the efficacy of topiramate at low dosage for alcohol dependence. The use of topiramate at low dosage could increase the number of subjects in treatment, given the reduced possibility of adverse events.

Patients with impulse control deficits often show cognitive abnormalities especially in executive abilities. One possibility to examine the underlying neurophysiological mechanisms is to assess evoked potentials. In the present study an adapted go/nogo-paradigm was used to investigate electrophysiological correlates of voluntary selection and behaviour control processes in patients suffering from alcohol dependence and attention deficit hyperactivity disorder (ADHD).

15 patients with alcohol dependence, 15 adult patients with ADHD and 15 control persons were included into the study. Patients with alcoholism were examined twice: before and after an inpatient detoxification.

The participants performed a go/nogo task, comprising three different conditions:

Apart from the go-condition (button press required) and the nogo-task (inhibition of a behavioural response), a voluntary selection task was included in which participants were allowed to freely decide, whether to press the response button or not.

Response inhibition and voluntary selection processes were related to a fronto-central negativity after 200 ms (N2) and a positivity after 300 ms (P3) in healthy subjects. In patients, the P3 amplitude was reduced compared to the controls. In addition, alcohol dependent patients did not show a N2 potential.

The results indicate fronto-central dysfunctions dysfunctions in either patient group. However, different neuronal processes seemed to be affected in patients with ADHD and patients with alcoholism.

The problem of alcohol use is a major public health problem in the general students’ population in Belarus. We therefore screen for the prevalence and trace the order of increase in alcohol use and related problems among freshmen and seniors in Belarusian universities.

A total of 565 (1st - 2nd courses, mean age - 18.9yrs), 537 (3rd - 4th courses, mean age - 20.9yrs) and 397 (5th - 6th courses, mean age - 22.8 yrs) university students in Minsk (Belarus) were administered the AUDIT questionnaire, including other alcohol related questions. The cut-off point on the AUDIT was set at 8. All statistical analyses were performed using SPSS 16.0 version for Windows; the criteria of Pearson, X2 and Student's t testsñ. The probability value for significance was set at p< 0.05.

Alcohol use and related problems increased with increase in the average age and year of study. In the 1st - 2nd, 3rd - 4th, 5th - 6th courses, alcohol users were 83.56%, 85.64%, 94.22% respectively and problem drinkers were 14.51%, 17.88%, 20.91% respectively. The use of strong strength alcoholic beverages was linked with a high risk of alcohol related problems, than the use of weak alcoholic beverages in the general students’ population.

The level of alcohol use and related problems in the general students’ population in Belarus are high and show increase in order of increase both in the average age and in the year of study.

A number of studies have shown variations in the rate of alcohol and substance use disorders among different occupations, but no study till now stressed on such a variation in Iraq. The present study aimed to study variations in the rate of alcohol and substance use disorders between journalists and some other occupations in Erbil city.

200 journalists and 486 of other professionals were interviewed between the period of September to November 2008 by a structured interview (M.I.N.I.) for the detection of alcohol and substance use disorders.

Among the journalists, 34.5% were alcohol dependents, 7.5% were alcohol abusers, 1% was substance dependent, and another 1% was substance abuser. Among the non-journalists, 7.6% were alcohol dependents, 2.26% were alcohol abusers, 1.44% was substance dependents, and 1.02% was substance abusers. Most of the substances, other than alcohol, used by both groups were the prescription pills. 50% of journalists and 75% of non-journalists, who were either substance dependents or abusers, were alcohol dependents or abusers at the same time. Male gender and those who achieve higher educational levels were more affected in both groups.

The present study concluded that occupation is an important determinant for alcohol and substance use disorders in Iraq. Working as a journalist, is a risk factor particularly for alcohol dependence. Gender is an important determinant within each occupation as well.

To evaluate the effect of pregabalin as a tapering therapy over the subjective sleep quality of patients who underwent a benzodiazepine withdrawal program.

This was a secondary analysis of a 12-week, prospective, and observational study carried out in patients aged 18 years or over, who met DSM-IV-TR criteria for benzodiazepine dependence without other major psychiatry disorder. Evaluations included the Benzodiazepine Withdrawal Symptom Questionnaire, the Hamilton Anxiety Rating Scale, the Clinical Global Impression scale, and the MOS-Sleep Scale. Changes from baseline to the endpoint in the different scales’ scores as well as correlations of these changes with those of the MOS-Sleep scores were calculated.

282 patients met the criteria for analysis. Mean pregabalin dose was 315 (166) mg/day at end-of-trial. We observed a significant and clinically relevant improvement in sleep outcomes at the study endpoint as measured with the MOS-Sleep Summary Index, that was reduced from 55.8 (18.9) pts at baseline to 25.1 (18.0) pts at week 12 (55% reduction), as well as with the six dimensions of the MOS-Sleep Scale. Moderate correlations were observed between Summary Index and sleep domains with improvements in the anxiety symptoms and in the disease severity as well. Also, sleep ameliorations were observed in the 52% successfully benzodiazepines withdrawals but, although to a lesser extent, in the remaining failures as well.

Pregabalin treatment improves subjective sleep quality in patients who underwent a benzodiazepine withdrawal program and this effect appears partly independent of the improvement of anxiety or withdrawal symptoms.

Cocaine consumption can induce transient psychotic symptoms, expressed as paranoia or hallucinations. Cocaine induced psychosis (CIP) is common but not developed in all cases.

To describe the Risk Factors for developing cocaine-induced psychosis in cocaine dependent patients, according DSM-IV-TR criteria.

This is the first European study about the relationship of CIP with consumption pattern variables and personality disorders, we evaluated 220 cocaine dependents over 18 years, 80'5% males, mean age 33.9 years (SD = 7.6). Patients were recluted from an outpatient clinic department and subsequently systematically evaluated using SCID I and SCID II interviews for comorbidity disorders, and a clinical-based systematic psychotic symptoms form.

A high proportion of cocaine dependent patients reported psychotic symptoms (51.8%) under influence of cocaine. The most frequent reported psychotic symptoms were paranoid beliefs and suspiciousness (42.4%). After a logistic regression analysis we found that a model consisted of high cocaine consumption (mean of 12.01 grams per week), cannabis dependence history and to use intranasal or smoked rout of administration had a sensitivity of 63.2% and a specificity of 70.2%.

We conclude that is relevant to evaluate CIP in patients consuming high amounts of cocaine, with cannabis dependence history and who do not use intranasal rout. It could be useful for preventing consequences or risks of psychotic states for themselves or others.

Until now, no reliable biological markers of risk and relapse in substance-dependent patients have been identified. The yawn-inducing test with apomorphine has been proposed as a marker of the functional status of the dopaminergic system and therefore a predictor of suffering an addiction or predisposition to relapse.

Studying the safety and efficacy of apomorphine test as a predictor of relapse in intranasal cocaine dependent, diagnosed according to DSM-IV-TR.

We performed the test of apomorphine at the beginning (day 1) and end (day 11/12) of a detoxification program in 33 patients (29 men). The majority of patients relapsed after 22 weeks of follow up (87% relapse). The average yawns in the sample were 10.9 ± 9.3 in the initial test (Apo 1) and 10.2 ± 10.2 in the final test (Apo 2). The 42% of patients relapsed early (before 4 weeks) and 45% late (afther 4 weeks). 58% of the sample (N = 19), which did not fall belatedly filled an average of 8.0 yawns in Apo1 and 8.1 on Apo2 and 42% who did so early (N = 14), 14,8 in Apo1 and 14.6 in Apo2. Therefore there are an increased number of yawns in patients with early relapse. No important side effects were reported.

Patients with early relapse have a higher number of yawns that those falling late or abstainers The apomorphine test is a safe test and it is a readily applicable tool in clinical practice and may be a biological marker of risk.

To retrospectively identify differences in antisocial and delinquent behavior between siblings discordant for serious substance use disorders.

Research has suggested that people who develop serious substance use disorders have delinquent traits as children prior to using any illicit drugs.

A retrospective survey was conducted of 50 pairs of adult siblings who were discordant for serious substance use disorders. The self-report early delinquency scale (SRED) was used to retrospectively assess delinquent traits in childhood and adolescence.

The mean SRED 29 (illegal item) score in treatment seeking opiate dependent people (mean age= 33.5 years) was 19.6 (SE=0.9) compared to 4.8 (SE=0.6) in same sex, non-substance dependent siblings (p< 0.0001; paired Wilcoxon test). The mean SRED 58 (norm violation) score in treatment seeking opiate dependent people was 36.8 (SE=1.7) compared to 10.5 (SE=1.4) in same sex siblings (p< 0.0001; paired Wilcoxon test). 40% of patients were expelled from school compared to 12% of siblings (Yates-corrected Chi2 = 8.78; p = 0.003). 96% of patients reported problems with the police as adolescence compared to 48% of controls (Yates-corrected Chi2 = 26.24; p < 0.0001). Police problems in substance users pre-dated first use of illicit substances by 5.5 years.

The study used a validated instrument and objective reports to confirm significantly higher rates of delinquent behavior and social dysfunction in childhood for substance users compared to non-substance dependent siblings. The delinquent behaviors usually predated serious substance misuse.

The present research is designed and performed by the aim of comparative study of psychological health level, probability of drugs addiction in girl and boy university students.

Random sample includes 200 persons who 120 persons were girl and 80 persons were boy university students who were compared. All students, General health Questionnaire (GHQ) and Probability of Self-suicide and Probability of Drugs Addiction (PSSPDA) have been deducted from central office of science Ministry consultation questionnaire.

Independent T-test was used; Test results show that anxiety level, depression, physical complaints and disturbed social interaction is meaningfully greater more severe in girl university students than boy university students. Also, results showed that drugs addition in boy university students is meaningfully greater than in girl university students. Also, probability of self-suicide risk is meaningfully greater in girl university students than boy university students.

Findings indicated that most university students who embark to self-suicide or come to addict drugs, are worry about their educational improvement and situation and most persons who commit to self-suicide, are affected by emotional problems such as depression, anxiety and unpleasureable relationships, addiction to drugs and alcohol, unemployment, loneliness and guilt emotions. Therefore, it could be said that transfer nature of lives of most university students is accompanied by the experience of stress exposure for them. In this way, most students are accompanied by stress exposure experience. In this way, most university students come to addict drugs in order to decrease the stress.

We investigated:

1. 1) the effects of PAE on the number of 5-HT neurons in the brainstem in female adult rats;

2. 2) the potential influence of ovarian sex steroids, estradiol (E2) and progesterone (P4) on this population of 5-HT neurons.

Female offspring from prenatal ethanol (PAE), pair-fed (PF) and ad lib-fed control (C) dams were studied in adulthood. Females were assigned to the following groups: 1) ovariectomized (OVX); 2) ovariectomized with estradiol replacement (OVX+E2; mean plasma concentration: 64 pg/ml); 3) ovariectomized and replaced with estradiol (as above) and progesterone (OVX+E2+P4; mean plasma concentration for P4:12 ng/ml); 4) Sham surgery (SHAM). Immunocytochemistry for 5-HT was performed.

PAE decreased the number of 5-HT-ir neurons in the dorsal raphe (DR) in OVX females. There was no effect of PAE the number of DR 5HT-ir neurons in OVX+E2 group, suggesting a possible neuroprotective role of estradiol in PAE animals. Treatment with both progesterone and estradiol compared to estradiol alone caused a further decrease in number of DR 5-HT-ir neurons in PAE but not C or PF animals.

These results provide evidence of the enduring effects of PAE on the serotonergic system, and suggest a role for the ovarian sex steroids in mediating these effects.

IMPART (CIHR) to JHS, NIH/NIAAA AA007789 and HELP to JW.