The serotonin 2C receptor agonist Ro-60-0175 attenuates effects of nicotine in the five-choice serial reaction time task and in drug discrimination.
BACKGROUND
There is evidence that serotonin(2C) (5-HT(2C)) receptors can modulate some behavioural effects of nicotine, but the generality of this action is not known.


OBJECTIVE
To analyse the influence of the 5-HT(2C) agonist Ro-60-0175 on responses to nicotine in the five-choice serial reaction time task (5-CSRTT) and on its discriminative stimulus effect; these procedures constitute models for attention-enhancing and subjective effects of nicotine, respectively.


METHODS
In the 5-CSRTT, rats were trained to obtain food reinforcers by detecting light stimuli and then challenged with Ro-60-0175 (0.3-0.8 mg/kg) and nicotine (0.2 mg/kg). For drug discrimination studies, rats were trained to discriminate nicotine (0.2 mg/kg) from saline in a two-lever procedure using a tandem schedule of food reinforcement.


RESULTS
In the 5-CSRTT, nicotine positively influenced most response indices, confirming previous results. Ro-60-0175 increased response latencies and omission errors and reduced anticipatory responding but had little effect on response accuracy; importantly, it counteracted the effects of nicotine on response speed and omission errors. Pentobarbitone (10-14 mg/kg) also slowed performance of the 5-CSRTT but did not weaken the nicotine-induced enhancement of performance. In the drug discrimination procedure, Ro-60-0175 was not generalised with nicotine but shifted the nicotine dose-response curve to the right in a dose-related manner.


CONCLUSIONS
The data suggest that selective occupancy of 5-HT(2C) receptors can attenuate some effects of nicotine in the 5-CSRTT and weaken the nicotine discriminative stimulus; these effects cannot be explained by a sedative action of Ro-60-0175.
Quarta
Davide
D
Section of Behavioural Pharmacology, Institute of Psychiatry P049, King's College London, De Crespigny Park, London, UK.
Naylor
Christopher G
CG
Stolerman
Ian P
IP
D000818:Animals; D003216:Conditioning, Operant; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000494:pharmacology*; D005731:Ganglionic Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects*; D058826:Serotonin 5-HT2 Receptor Agonists
D005021:Ethylamines; D005731:Ganglionic Stimulants; D006993:Hypnotics and Sedatives; D007211:Indoles; C103848:Ro 60-0175; D058826:Serotonin 5-HT2 Receptor Agonists; D009538:Nicotine; D010424:Pentobarbital