Effects of d-amphetamine and DOI (2,5-dimethoxy-4-iodoamphetamine) on timing behavior: interaction between D1 and 5-HT2A receptors

Abstract

The results suggest that both 5-HT(2A) and D(1) receptors, but not D(2) receptors, are involved in d-amphetamine's effect on timing behavior in the free-operant psychophysical procedure. DOI's effect on timing is mediated by 5-HT(2A) receptors, but neither D(1) nor D(2) receptors are involved in this effect.

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

“…b Relative response rate on lever B. SKF-81297 displaced the psychometric function to the left; neither dose of haloperidol reversed this effect believed to entail D 2 -like receptor stimulation (Spyraki et al 1982;Velazquez Martinez et al 1995;Herrera and Velazquez Martinez 1997), and attenuate the effect of the direct D 2 -like receptor agonist quinpirole on T 50 in this schedule (Cheung et al 2007). The present results are similar to previous findings with d-amphetamine, whose ability to reduce T 50 in the freeoperant psychophysical procedure was reversed by SKF-83566 but not by haloperidol, implying D 1 -but not D 2 -like dopamine receptor involvement (Body et al 2006b;Cheung et al 2006). The sensitivity of temporal differentiation to D 1 -like dopamine receptor stimulation is also supported by the finding that the D 1 -like receptor partial agonist SKF-38393 reduced peak time in the fixed-interval peak procedure (Frederick and Allen 1996).…”

“…The effect was presumably in part mediated by D 1 -like receptors, as it was attenuated by SKF-83566 but not by haloperidol. Similarly, d-amphetamine has also been found to reduce overall response rate on this schedule, its effect being reversed by SKF-83566 but not by haloperidol (Body et al 2006b;Cheung et al 2006). The reduction of T 50 and the reduction of overall response rate are likely to reflect different underlying mechanisms, as the psychometric curve is derived from relative response rate data; a reduction in overall response rate may result in an increase in the Weber fraction, but not in a change in the value of T 50 (Chiang et al 2000a;Odum et al 2002).…”

“…The two parameters T 50 and e may be used to derive the Weber fraction, an index of the precision of temporal differentiation (see Killeen and Fetterman 1988;Gibbon et al 1997;Ho et al 2002). d-Amphetamine has been found to reduce T 50 in this schedule (Chiang et al 2000a;Body et al 2006b;Cheung et al 2006), an effect that is qualitatively similar to the effect of psychostimulants on performance on the fixed-interval peak procedure. Interestingly, this effect was reversed by the D 1 -like dopamine receptor antagonist SKF-83566, but not by the D 2 -like dopamine receptor antagonist haloperidol (Body et al 2006b;Cheung et al 2006), indicating an involvement of D 1 -like dopamine receptors in d-amphetamine's effect on timing in this schedule.…”

Animal Models of Serotonergic Psychedelics

“…However, the selective dopamine D 1 receptor antagonist SKF-83566 blocks the effect of amphetamine, but not DOI, on this task. 106 An opposite pattern of errors was observed in the time discrimination task (which is a retrospective timing task), as DOI decreased the percentage of responses on lever B at longer durations. 107 This highlights how similar tasks my produce varying and seemingly contradictory conclusions.…”

“…106 The effects of both DOI and amphetamine on timing performance are reversed by the 5-HT 2A receptor antagonist MDL-100907. However, the selective dopamine D 1 receptor antagonist SKF-83566 blocks the effect of amphetamine, but not DOI, on this task.…”