Evidence of cross-tolerance between behavioural effects of nicotine and cocaine in mice.
BACKGROUND
Studies have reported that chronic exposure to nicotine does not alter the effects of cocaine on locomotor activity, and vice versa. However, the apparent lack of effect of one drug on the behavioural response to the other may be due to an exclusive focus on locomotor activity as the target behaviour.


OBJECTIVE
To test whether repeated pretreatment with nicotine causes tolerance or sensitization to cocaine's effects on diverse behaviours: locomotion, rearing, grooming, and immobility. Similarly, the effects of repeated cocaine treatment on the acute response to nicotine were also tested.


METHODS
Mice were pretreated with 14 injections of nicotine (0.3 mg/kg), cocaine (5 mg/kg) or saline, the injections being given once daily, except for three breaks of two days each. Two days after the final pretreatment injection, mice were given a challenge injection of saline, cocaine (3 or 5 mg/kg) or nicotine (0.3 or 1 mg/kg), and observed in a large test cage for 40 min using a time-sampling procedure.


RESULTS
Repeated administration of either drug produced some tolerance to subsequent challenge with the same dose of the drug. Prior nicotine exposure significantly attenuated cocaine-induced decreases in grooming and increases in rearing, but did not significantly affect other behaviours. In contrast, prior cocaine exposure failed to alter nicotine's effects on any behaviour.


CONCLUSIONS
Cross-tolerance between nicotine and cocaine (but not vice-versa) can be demonstrated if several behaviours are observed; measures of locomotor activity are less sensitive to the effect. The asymmetrical pattern of cross-tolerance may be due to differential inhibition of dopamine uptake by the two drugs.
Desai
Rajeev I
RI
School of Psychology, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. rdesai@intra.nida.nih.gov
Terry
Philip
P
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology
D017448:Receptors, Dopamine D2; D009538:Nicotine; D003042:Cocaine