REPEATED D-AMPHETAMINE ENHANCES STIMULATED MESOAMYGDALOID DOPAMINE TRANSMISSION

The mesoaccumbens dopamine pathway exhibits an enhanced dopaminergic r esponse to a challenge injection of cl-amphetamine or cocaine after re peated intermittent exposure to that drug. Much research has focused o n the potential role of this sensitised response in the enhanced prope nsity of drug-associated stimuli to elicit relapse. However the amygda la is acknowledged to play a critical role in stimulus-reward learning , and recent work suggests that the mesoamygdaloid dopamine pathway ex erts a significant influence upon amygdala function. In the present st udy, rats were administered d-amphetamine (1 mg/kg, IF) or vehicle onc e per day, for 14 days. After 11 untreated days, a locomotor assay sho wed that prior repeated administration of cl-amphetamine led to a mark edly enhanced locomotor response to 0.5 mg/kg d-amphetamine. There was no effect of d-amphetamine pretreatment upon the response to a novel environment, or to injection with vehicle. Following a total of 14 day s in the home cage, subjects were implanted with microdialysis probes within the amygdala, and for comparison also within the nucleus accumb ens. Baseline and cl-amphetamine-stimulated (0.5 mg/kg) levels of extr acellular dopamine were assessed for each brain region. Results showed that baseline levels of dopamine were very similar in sensitised and control animals. By contrast, prior treatment with cl-amphetamine enha nced dopamine overflow in response to a challenge with d-amphetamine b oth in the nucleus accumbens and amygdala. These results indicate that changes in the pattern of dopamine transmission both in the nucleus a ccumbens, and the amygdala, accompany the behavioural sensitisation ob served after repeated exposure to d-amphetamine. Hence, an enhanced pr opensity of drug-associated stimuli to elicit relapse may not depend s olely upon changes relating to the mesoaccumbens dopamine projection.