5-HT(1A) RECEPTOR AGONISTS INDUCE ANTEROGRADE AMNESIA IN MICE THROUGHA POSTSYNAPTIC MECHANISM

The effect of the 5-HT1A receptor partial agonist tandospirone on memo ry was investigated in mice using a single trial, step-through passive avoidance task. Tandospirone disrupted performance in a dose-dependen t manner when administered before the training trial but not when inje cted immediately post-training. The pre-training effect was not the re sult of reduced responsiveness to foot shock because tandospirone did not alter current threshold intensity to elicit flinch, run and vocali zation responses. The performance deficit was alleviated by treatment with d-amphetamine prior to the retention test. The memory impairment by tandospirone was mimicked by the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-dipropylaminotetralin HBr) and blocked by the 5-HT1A recept or antagonist BMY7378 erazinyl]ethyl]-8-azaspirol-[4]-decane-7,9-dione ). BMY7378 alone was ineffective. Treatment with the 5-HT synthesis in hibitor PCPA (parachlorophenylalanine) resulted in apparent enhancemen t rather than disruption of the avoidance behavior. However, the anter ograde amnestic effects of tandospirone and 8-OH-DPAT were not affecte d by PCPA, and lack of interactions between PCPA and the 5-HT1A agonis ts revealed in the statistical analyses indicated that the effects of PCPA were not mediated by 5-HT1A receptors. It is concluded that 5-HT1 A receptor agonists and partial agonists produce a reversible anterogr ade amnesia that is mediated by postsynaptic 5-HT1A receptors.