Effects of 5-HT drugs in prefrontal cortex during memory formation and the ketamine amnesia-model

This article describes a series of experiments investigating the effects of systemic or intraprefrontal administration of serotonergic agents on ketamine induced memory deficits in rats. First, rats were trained on an operant autoshaping task. immediately after training, rats drug were injected with different doses of drug or saline. Following administration, rats were tested after 1.5 h for short-term memory (LTM) of conditioned response. (STM) and 24 h for long-term memory An increase or decrease in number of conditioned responses was an index of retention. The major results of this work show that ketamine impaired STM and this effect was reversed, by either systemic or intra prefrontal cortex administration of the agonist 5-HT1A/7 8-OH-DPAT, the 5-HT receptor. antagonists MDL100907 (S-HT2A), SB-399885 (5-HT6), and SB-269970 (5-HT7). The ketamine STM-impairment effect was not altered by the 5-HT1A antagonist WAY 100635 or the 5-HT1B antagonist SB-224289. Notably, prefrontal cortex inhibition of translation or transcription interrupted STM without affecting LTM suggesting different signaling mechanisms. The interacting effect of NMDA and serotonin area of study; both receptors are considered to be important targets for the development of antipsychotic medication. Particularly, 5-HT1A/7, 5-HT2A 5-HT6, and 5-HT7 receptors present in prefrontal cortex, represent development of drugs for the treatment of SMT-deficits. . (C) 2008 Wiley-Liss, Inc.