Studies on the Role of Mesolimbic Dopamine in Behavioural Responses to Chronic Nicotine

Abstract

Three procedures, in vivo microdialysis in conscious freely moving rats; 6-hydroxydopamine lesions of the nucleus accumbens and operant avoidance conditioning, have been used to investigate the possible role of the mesolimbic dopamine (DA) system in the behavioural responses to chronic nicotine (0.4 mg/kg). The dialysis studies showed that pretreatment with nicotine for 5 days enhanced its ability to stimulate DA secretion in the nucleus accumbens and that this effect corresponded with an increased locomotor response to the drug. Since the lesion studies revealed that the stimulatory effects of chronic nicotine on locomotor activity are abolished by lesions of the mesolimbic system, the data appear consistent with the hypothesis that the increase in locomotor activity evoked by pretreatment with nicotine may be related to the enhanced mesolimbic DA response to nicotine. The results of the operant conditioning study showed that the effects of d-amphetamine (0.5 mg/kg) on the acquisition and performance of an unsignalled shock avoidance task were very similar to those of nicotine and that, as is the case for nicotine, amphetamine-withdrawal caused a disruption of avoidance performance. Since, in addition, d-amphetamine was able to attenuate the effects of nicotine-withdrawal, the data suggest that, in this avoidance model of nicotine dependence at least, the animals may become dependent upon increased levels of DA secretion evoked by the drugs in order to perform the task efficiently.