Behavioral sensitization to nicotine is associated with behavioral disinhibition; counteraction by citalopram.

This study investigated the effects of repeated nicotine treatment on locomotor activity and behavioral inhibition, and the influence of citalopram on the behavioral effects obtained. Male rats received daily subcutaneous injections of vehicle + vehicle (veh + veh), citalopram (5.0 mg/kg) + vehicle (cit + veh), vehicle + nicotine (1.0 mg/kg; veh + nic) or citalopram + nicotine (cit + nic). Acutely, nicotine stimulated locomotor activity, and repeated daily nicotine injections sensitized veh + nic rats to the nicotine-induced locomotor stimulation after 5, 10 and 15 treatment days, whereas in cit + nic rats, the enhancement of nicotine-induced locomotion was suppressed. However, when challenged with nicotine after citalopram withdrawal (-36 h), the cit + nic treated animals were also observed to be sensitized. In the elevated plus-maze, repeated nicotine treatment produced behavioral disinhibition, measured as an increase of time spent in and entries made into open arms (%), and chronic citalopram treatment attenuated the expression of behavioral disinhibition. Moreover, the degree of nicotine sensitization correlated to the behavioral disinhibition observed. In summary, these findings suggest that behavioral sensitization to nicotine is associated with behavioral disinhibition and that chronic citalopram treatment counteracts the expression of both phenomena. Since citalopram is a highly selective serotonin reuptake inhibitor, the effects of citalopram may be due to a facilitation of serotonin neurotransmission caused by the chronic citalopram treatment.