title: Effects of dopamine receptor antagonists on nicotine-induced attentional enhancement.
abstract: An understanding of the neuropharmacological mechanisms mediating attentional enhancement by nicotine would indicate whether these effects could be dissociated pharmacologically from other behavioural effects of nicotine. The aim of the present study was to examine the involvement of dopamine neurotransmission in the effects of nicotine on different response indices of an attentional paradigm. The effects of the D2-type dopamine receptor antagonist raclopride (0.025-0.1 mg/kg) and the D1-type receptor antagonist SCH23390 (0.006-0.024 mg/kg) were tested, in both the presence and absence of nicotine (0.1 mg/kg), in rats trained in a modified version of the five-choice serial reaction time task (5-CSRTT). Nicotine robustly enhanced the accuracy of signal detection, reduced omission errors and shortened response latencies. Neither raclopride nor SCH23390 altered the effects of nicotine on accuracy and omissions, but raclopride augmented accuracy and SCH23390 increased omissions when given alone. By contrast, raclopride, but not SCH23390, reversed the nicotine-induced reductions in response latencies, at doses that had no effect on their own. In the presence of nicotine, both antagonists had rate-disruptive effects at the highest dose. Both antagonists also reduced responding in the intertrial interval, and this effect was additive to the nicotine-induced decrease in this measure. The data indicate that D2-type dopamine receptors may be involved in the effects of nicotine on response speed. Neither the D1- nor the D2-type dopamine receptor antagonist affected nicotine-induced improvements in signal detection, at doses that reversed dependence-related behavioural effects of nicotine in previous studies. Thus these effects may be pharmacologically dissociable.
authors.affiliation: Section of Behavioural Pharmacology, P049, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. b.hahn@iop.kcl.ac.uk
authors.forename: B
authors.initials: B
authors.lastname: Hahn
authors.forename: M
authors.initials: M
authors.lastname: Shoaib
authors.forename: I P
authors.initials: IP
authors.lastname: Stolerman
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018722:Nicotinic Agonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D020891:Raclopride; D009538:Nicotine; D004298:Dopamine