Effects of a 5-HT2 receptor agonist, DOI (2,5-dimethoxy-4-iodoamphetamine), and antagonist, ketanserin, on the performance of rats on a free-operant timing schedule

Abstract

This experiment examined the effect of a 5-HT2 receptor agonist DOI (2,5-dimethoxy-4-iodoamphetamine), and antagonist, ketanserin, on temporal differentiation performance. Twelve rats were trained under the free-operant psychophysical procedure to press two levers (A and B) in 50-s trials in which sucrose reinforcement (0.6 mol/l, 50 microl) was provided intermittently for responding on A during the first half, and on B during the second half of the trial. Psychometric curves were derived from percent responding on B (%B), recorded in successive 5-s epochs of the trials; logistic functions were fitted to these data for the derivation of timing indices (T50 [time corresponding to %B=50%], epsilon [slope of the logistic curve], Weber fraction). Cumulative probability of switching in successive 5-s epochs was used to estimate the mean switching time, S50. DOI (0.0625, 0.125 and 0.25 mg/kg, s.c.) dose-dependently reduced T50 and S50. These effects of DOI (0.25 mg/kg) were antagonized by ketanserin (1.0 mg/kg). The results show that DOI alters temporal differentiation in the free-operant psychophysical procedure. The antagonistic effect of ketanserin indicates that the effect of DOI was probably mediated by 5-HT2A rather than 5-HT2C receptors, since ketanserin is relatively selective for 5-HT2A receptors. Comparison of these results with our previous findings with a 5-HT1A receptor agonist indicates that 5-HT1A and 5-HT2A receptors mediate qualitatively similar effects on temporal differentiation.

Psychedelics

“…They also suggest the possibility that stimulus control is relatively weak and may be more vulnerable to disruption at longer stimulus durations. These results are similar to those of Body et al (2003), who found that DOI also altered temporal differentiation in the freeoperant psychophysical procedure in rats, an effect that was similarly blocked by ketanserin. Asgari et al (2006b) examined the effect of (2)-DOI (0.25 mg/kg, s.c.) on the fixed-interval peak procedure in 18 female rats.…”

Evidence for the sensitivity of operant timing behaviour to stimulation of D1 dopamine receptors

“…In agreement with previous findings using Stubbs' freeoperant psychophysical procedure (Stubbs 1976;White 1994a, b, 1997;Chiang et al 1998Chiang et al , 1999Chiang et al , 2000aMachado and Guilhardi 2000;Body et al 2002Body et al , 2003Body et al , 2004Body et al , 2006aCheung et al 2006), response rate on lever A declined, while response rate on lever B increased, as a function of time from trial onset, this being reflected in an increasing percentage of total responding being devoted to lever B (%B) as the trial progressed. The absolute rate of responding on lever B tended to decline towards the end of the trial.…”

“…Moreover, SKF-81297 (0.2 and 0.4 mg kg −1 ) reduced overall response rate without affecting T 50 , indicating that a change in T 50 was not an inevitable consequence of a reduction of response rate. Finally, previous experiments on the effects of drugs acting at 5-hydroxytryptamine 5-HT receptors have demonstrated dissociation of effects of drugs on response rate and T 50 (Body et al 2003(Body et al , 2004.…”

Attenuation of nicotine?s discriminative stimulus effects in rats and its locomotor activity effects in mice by serotonergic 5-HT2A/2C receptor agonists

“…The antagonism tests with ketanserin demonstrated that it could reverse the attenuation of the nicotine stimulus produced by DOI. Ketanserin is a 5-HT antagonist that acts at the 5-HT 2A receptor (Body et al 2003), although it may also have activity at the 5-HT 2C receptor (Glennon et al 2002). The ketanserin results suggest that the 5-HT 2A receptor subtype is playing an important role in the attenuation of the discriminative stimulus effects of nicotine by DOI, although at this time it is unclear exactly what this role is.…”