RATIONALE: Temporal differentiation refers to animals' ability to regulate their behaviour during an ongoing interval. Striatal dopaminergic mechanisms are purported to be involved in temporal differentiation, and recent evidence also implicates 5-hydroxytryptaminergic (5-HTergic) mechanisms, possibly mediated by 5-HT(2A) receptors. There is evidence that 5-HT(3) receptors contribute to the regulation of dopamine release in the basal ganglia; however, it is not known whether 5-HT(3) receptor stimulation can influence temporal differentiation. OBJECTIVE: We examined the effects of a selective 5-HT(3) receptor agonist m-CPBG, a mixed 5-HT(2A/3) receptor agonist quipazine, and selective 5-HT(3) and 5-HT(2A) receptor antagonists (MDL-72222 and ketanserin, respectively) on temporal differentiation in a free-operant psychophysical procedure. METHODS: Twenty-four rats were trained to respond on two levers (A and B) under a free-operant psychophysical schedule, in which sucrose reinforcement (0.6 M: , 50 microl) was provided intermittently for responding on A during the first half and on B during the second half of 50-s trials. Logistic psychometric functions were fitted to the relative response rate data [percent responding on B (%B) vs time from trial onset (t)], and quantitative indices of timing performance [T (50) (value of t corresponding to %B=50), Weber fraction, and mean time of switching from A to B, S (50)] were derived. RESULTS: Quipazine (0.5, 1, and 2 mg kg(-1)) altered timing performance, dose-dependently reducing T (50) and S (50); m-CPBG (2.5, 5, and 10 mg kg(-1)) had no significant effect. The effect of quipazine was antagonized by ketanserin (2 mg kg(-1)), but not by MDL-72222 (1 mg kg(-1)). CONCLUSIONS: The present results provide no evidence for the involvement of 5-HT(3) receptors in temporal differentiation and indicate that the effect of quipazine on performance was mediated by 5-HT(2A) receptor stimulation. The results are consistent with previous evidence for the involvement of 5-HT(2A) receptors in interval timing behaviour.
RATIONALE: Temporal differentiation refers to animals' ability to regulate their behaviour during an ongoing interval. Striatal dopaminergic mechanisms are purported to be involved in temporal differentiation, and recent evidence also implicates 5-hydroxytryptaminergic (5-HTergic) mechanisms, possibly mediated by 5-HT(2A) receptors. There is evidence that 5-HT(3) receptors contribute to the regulation of dopamine release in the basal ganglia; however, it is not known whether 5-HT(3) receptor stimulation can influence temporal differentiation. OBJECTIVE: We examined the effects of a selective 5-HT(3) receptor agonist m-CPBG, a mixed 5-HT(2A/3) receptor agonist quipazine, and selective 5-HT(3) and 5-HT(2A) receptor antagonists (MDL-72222 and ketanserin, respectively) on temporal differentiation in a free-operant psychophysical procedure. METHODS: Twenty-four rats were trained to respond on two levers (A and B) under a free-operant psychophysical schedule, in which sucrose reinforcement (0.6 M: , 50 microl) was provided intermittently for responding on A during the first half and on B during the second half of 50-s trials. Logistic psychometric functions were fitted to the relative response rate data [percent responding on B (%B) vs time from trial onset (t)], and quantitative indices of timing performance [T (50) (value of t corresponding to %B=50), Weber fraction, and mean time of switching from A to B, S (50)] were derived. RESULTS:Quipazine (0.5, 1, and 2 mg kg(-1)) altered timing performance, dose-dependently reducing T (50) and S (50); m-CPBG (2.5, 5, and 10 mg kg(-1)) had no significant effect. The effect of quipazine was antagonized by ketanserin (2 mg kg(-1)), but not by MDL-72222 (1 mg kg(-1)). CONCLUSIONS: The present results provide no evidence for the involvement of 5-HT(3) receptors in temporal differentiation and indicate that the effect of quipazine on performance was mediated by 5-HT(2A) receptor stimulation. The results are consistent with previous evidence for the involvement of 5-HT(2A) receptors in interval timing behaviour.
Authors: S S al-Zahrani; M Y Ho; D N Velazquez Martinez; M Lopez Cabrera; C M Bradshaw; E Szabadi Journal: Psychopharmacology (Berl) Date: 1996-10 Impact factor: 4.530
Authors: Adam L Halberstadt; Ivan S Sindhunata; Kees Scheffers; Aaron D Flynn; Richard F Sharp; Mark A Geyer; Jared W Young Journal: Neuropharmacology Date: 2016-03-25 Impact factor: 5.250