Some antipsychotics act as partial agonists on serotonin-1A receptors (5-HT1AR) localized postsynaptically in cortex and hippocampus and presynaptically on the serotonergic cell bodies and dendrites in raphe nuclei.
Our study's aim was to investigate the effect of pre- and postsynaptic 5-HT1AR activation on MK-801 (0.1, 0.3 mg/kg)-induced sensorimotor gating deficits and hyperlocomotion in a rat model of schizophrenia-like behavior. To investigate the effect of presynaptic receptor activation we used a partial agonist (buspirone; 1,10 mg/kg) and a low dose of full agonist (8-OH-DPAT; 0.025 mg/kg). The effect on both pre- and postsynaptic receptors was investigated by a high dose of full agonist (8-OH-DPAT; 1 mg/kg).
We found that buspirone in both doses had no effect on MK-801-induced deficit in senzorimotor gating. Contrarily, the low dose of 8-OH-DPAT ameliorated the deficit. The MK-801-induced hyperlocomotion was decreased by buspirone as well as by the low dose of 8-OH-DPAT. Activation of both pre- and postsynaptic 5-HT1AR had an opposite effect on MK-801-induced behavior.
Our findings accord with the published results that partial 5-HT1AR agonists could be effective in schizophrenia treatment, but full potent agonists could exacerbate psychotic symptoms. Observed differences between buspirone and the low dose of 8-OH-DPAT could be due to inhibition of D2 receptor.
This research was supported by grant MZ0PCP2005 from the MZCR and by the projects 1M0517 from the MSMT