On the role of catecholamines in the reinforcing and punishing properties of stimulants and opiates

The role of ascending catecholamine systems in the punishing and reinforcing properties of some opiates and stimulant drugs was investigated. In one series of experiments, the reinforcing properties were evaluated through the use of intravenous self-administration procedures while the punishing properties were evaluated through the conditioned taste aversion procedure. In one experiment fifteen rats were trained to press a lever to receive an intravenous injection of cocaine and after this behaviour had stabilized, each rat received bilateral intracerebral injections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the n. accumbens. These lesions produced a marked disruption of cocaine self-administration which in most cases returned to baseline rates after 1-3 weeks. This recovery was found to be negatively correlated with the levels of dopamine (DA) remaining in the n. accumbens (r=-.81). The animals with the severest depletion of DA failed to show recovery of cocaine intake. This disruption of cocaine self-administration behaviour was shown not to be due to a non-specific effect on operant responding, because the same animals which failed to self-administer cocaine continued to self-administer apomorphine at pre-lesion rates. To evaluate whether noradrenergic (NA) mechanisms serve a critical role in cocaine self-administration, four rats received two bilateral injections of 6-OHDA aimed at the dorsal and ventral NA bundles. Despite causing near total depletion of forebrain NA, these lesions did not significantly affect the rate or pattern of cocaine self-administration. These data do not support the hypothesis that forebrain NA mechanisms subserve stimulant-based reinforcement, and the evidence in favor of such a view is discussed. In a separate series of experiments, it was observed that depletion of central DA and NA by intraventricular injections of 6-OHDA severely attenuated a conditioned taste aversion (CTA) induced by amphetamine. This attenuation was not the result of a general learning deficit because animals with identical treatments acquired a CTA when LiCl was used as the punishing stimulus. Selective depletion of hippocampal and cortical NA through intracerebral infusions of 6-OHDA, which spare DA systems, has no effect on an amphetamine-induced CTA. It is, therefore, argued that central DA, rather than NA, mechanisms are involved in the punishing property of amphetamine. The possibility that both the punishing and reinforcing effects of psychomotor stimulants may be mediated by the same systems in the brain is discussed. Depletion of forebrain NA was found to attenuate the CTA induced by 10 mg/kg morphine. This effect suggested some intriguing possibilities regarding NA and the reinforcing and punishing properties of opiates. Self-administration of heroin was not affected, however, by depletion of forebrain NA following 6-OHDA lesions, suggesting that forebrain NA does not play a critical role in opiate reinforcement. The DA receptor blocker, pimozide, was found to produce an apparent blockade of cocaine reinforcement, but pimozide had no effect on heroin self-administration. It therefore appears DA mechanisms are not critical to heroin reinforcement, and that there are multiple systems in the brain which can subserve drug reward.Graduate and Postdoctoral StudiesGraduat