Multiple 5-HT receptors in passive avoidance: Comparative studies of p-chloroamphetamine and 8-OH-DPAT

The Rim of this study tons to examine the involvment of multiple 5-HT recep tors in passive (PA) avoidance (PA) with a focus oil 5-HT,A, 5-HT2A, and 5- HT,,receptors, Because increases in 5-HT transmission result in concomitant multiple 5-HT receptor activation, the effects of the 5-HT releasing: comp ound p-chloroamphetamine (PCA) were compared with those of the selective 5- HT1A receptor agonist 8-OH-DPAT in the vat. In addition?, some results with the nonselective 5-HT2C/2B/1B receptor agonist mCPP are presented. When in jected before PA training, 8-OH-DPAT, mCPP, and PCA produced a dose-related impairment oft he 24-hour retention. The crucial involvement of the postsy naptic 5-HT1A receptors in the action of 8-OH-DPAT was confirmed. Thus, the 5-HT,, receptor antagonists WAY 100635 and (-)-pintdolol blocked the PA de ficit by 8-OH-DPAT. The impairment of PA caused by PCA was attenuated try W AY 100635 and (-)-pindolol, suggesting an involvement oft he 5-HT1A,, recep tor. In contrast, the 5-HT2A and 5-HT2C, receptors: were of negligible impo rtance in the 24-hour retention deficit induced by PCA. Ho However, the abi lity of the 5-HT,, receptor antagonist Ro 60-0491 to black the inhibitory e ffects of mCPP ir indicated an important regulatory role of the 5-HT2C rece ptor in PA. The nonselective 5-HT receptor antagonist methiothepin attenuat ed the PA deficit by PCA bit lacked activity versus 8-OH-DPAT. These data p rovide evidence for the hypothesis that, in addition to the 5-HT1A receptor , other 5-HT receptor subtypes are involved in the inhibitory actions of PC A. Importantly changes in dopamine transmission seemed not to contribute to the PA impairment by PCA. The behavioural alterations caused by the drug t reatments at the time of PA training could not be related to the subsequent retention performance conclusion, multiple 5-HT receptors are involved in PA with roles that probably differ at various stages of information process ing. These findings also suggest that there probably exists a functional di stinction between 5-HT receptor subtypes in different of types aversive lea rning. [Neuropsychopharmacology 22:168-190, 2000] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.