PubMed · 817329
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A Randrup, I Munkvad. 1975. Stereotyped behavior.. https://doi.org/10.1016/0306-039x(75)90027-6
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Both amphetamine and cocaine lead to an intake pattern in chronic addicts in which the drug is taken repeatedly over prolonged periods. While continuously administered amphetamines, designed to mimic this intake pattern, have a neurotoxic effect on caudate dopamine terminals, several studies have failed to find similar effects following continuous cocaine. In this study, these findings in striatum were replicated in rats using silver staining for degenerating neurons. But it was further found that either amphetamine or cocaine given continuously over a 3- to 5-day period induce a highly specific pattern of axonal degeneration extending from the lateral habenular nucleus along the fasciculus retroflexus towards the ventral tegmentum. This finding supports a rich literature on the involvement of these same pathways in the actions of dopamine agonists, reward mechanisms, and the integration of limbic, extrapyramidal, and midbrain centers.
Unilateral injections of 6-hydroxydopamine into the striatum resulted in almost immediate ipsilateral amphetamine (AMPH)- and delayed contralateral apomorphine (APO)-induced circling behavior in rats. APO-induced rotation correlated positively with that caused by AMPH. In these animals, there was an almost complete disappearance of dopamine uptake sites as well as increases in DA D2 receptors in specific subdivisions of the ipsilateral caudate-putamen (CPu). Both the rate of AMPH- and APO-induced rotation correlated with the percentage of DA terminal loss in the total aspect and in various quadrants of the striatum. In contrast, AMPH- and APO-induced rotation correlated with the percentage increase in striatal D2 receptors only in the dorsolateral (DL) aspect of the CPu. These results indicate that both AMPH- and APO-induced rotation can be used to determine the extent of DA terminal loss in the rat basal ganglia. The positive correlation of circling behavior to only changes in DA D2 receptors observed in the DL striatal subdivision provides further evidence for the heterogeneity of the basal ganglia. This model of hemiparkinsonism in the rat which uses a distant intrastriatal approach to the destruction of nigral DA cell bodies may be a more appropriate model to study the regenerative properties of the nigrostriatal DA system. This approach could also be used to more specifically localize peptidergic receptors on midbrain dopamine cell bodies.
Withdrawal of rats from chronic ethanol, morphine, cocaine and amphetamine resulted in a marked reduction in extracellular dopamine (DA) concentration in the ventral striatum as measured by microdialysis. Following ethanol and naloxone-precipitated morphine withdrawal, the time course of DA reduction paralleled that of the withdrawal symptomatology. On the other hand, following discontinuation of chronic cocaine, DA reduction was delayed by over 24 h but persisted for several days. After amphetamine withdrawal the fall in DA occurred more rapidly but the reduction also persisted for several days. The administration of the NMDA receptor antagonist, MK-801, to rats withdrawn from chronic ethanol, morphine or amphetamine, but not from chronic cocaine, readily reversed the fall in DA output. The reduction in extracellular DA during ethanol withdrawal was also reversed by SL 82.0715, another NMDA receptor antagonist.