New Findings on the Sensitivity of Free-Operant Timing Behaviour to 5-Hydroxytryptamine Receptor Stimulation

Abstract

Timing performance maintained under the free-operant psychophysical procedure (FOPP) is sensitive to 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptor stimulation. Agonists of these receptors displace the psychometric function towards shorter durations, reducing , the index of central tendency of timing. Here we report the effects of Ro-600175, a selective 5-HT2C receptor agonist, and mCPP, a 5-HT receptor agonist with high affinity for 5-HT2C receptors and lower affinity for 5-HT1A, 5-HT1B and 5-HT2A receptors, on timing behaviour. Rats were trained under the FOPP to press two levers (A and B) in 50-s trials in which reinforcers were provided intermittently for responding on A in the first half, and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 5-s epochs of the trials; logistic psychometric curves were fitted to the data from each rat under each treatment condition for derivation of timing indices [ (time corresponding to %B = 50%), Weber fraction]. The rats received systemic treatment with Ro-600175, mCPP, and mCPP in combination with antagonists of 5-HT1A (WAY-100635), 5-HT1B (isamoltane), 5-HT2A (MDL-100907) or 5-HT2C (SB-242084) receptors. mCPP (2.5 mg kg−1 i.p.), but not Ro-600175 (1, 2, 4 mg kg−1 i.p.), reduced . SB-242084 (0.6 mg kg−1 i.p.) potentiated mCPP’s effect on . mCPP’s effect on was not altered by isamoltane (8.0 mg kg−1 i.p.), but was attenuated by MDL-100907 (1.0 mg kg−1 i.p.) and WAY-100635 (0.1 mg kg−1 s.c.). The results suggest that mCPP’s effect on timing is mediated by an agonistic action at 5-HT1A and 5-HT2A, but not 5-HT1B, receptors. The role of 5-HT2C receptors is unclear, in view of SB-242084’s ability to potentiate the effect of mCPP, while Ro-600175 had no effect on . The possibility is considered that 5-HT2C receptors may counteract 5-HT1A and/or 5-HT2A receptor-mediated effects on timing performance.