The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801

The purpose of the present study was to investigate the opposite effect of the pre- and postsynaptic serotonin-1A (5-HT1A) receptors on the psychotic-like behavior induced by a non-competitive antagonist of the NMDA receptor, dizocilpine (MK-801). Male Wistar rats received two doses (0.025 mg/kg and 1 mg/kg) of 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin) and/or MK-801 in two different doses, 0.1 mg/kg or 0.3 mg/kg. We measured sensorimotor gating by testing prepulse inhibition of acoustic startle response (PPI) and locomotor activity of rats. We found an opposite effect of the low and high 5-HT1A receptor agonist doses on MK-801 induced deficit in PPI and hyperlocomotion in habituated rats. The low dose of 8-OH-DPAT, which preferentially acts on presynaptic 5-HT1A receptors, restored the deficit in PPI and hyperlocomotion in MK-801 (0.1 mg/kg)-treated habituated rats. However, the high dose of 8-OH-DPAT, which activates both pre- and postsynaptic 5-HT1A receptors, decreased PPI and increased locomotor activity after administration of the low dose of MK-801. Administration of 8-OH-DPAT itself dose-dependently decreased PPI. However, only the high dose of 8-OH-DPAT increased spontaneous locomotor activity of rats. Our results indicate that there is an interaction between the NMDA and 5-HT1A receptors. In addition, these findings could indicate that activation of the 5-HT1A autoreceptor could be effective as a treatment in schizophrenia, but full potent agonism of the receptor could worsen the psychotic symptoms. (c) 2006 Elsevier Ltd. All rights reserved.