Transport of dopamine in discrete areas of the striatum and of cerebral cortex in the rat.
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Biomedical subjects
Publications and source records attributed to L Stinus.
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The destruction of ascending noradreniergic pathways by bilateral microinjections of 6-hydroxydopamnine made laterally to the pedunculus cerebellaris superior completely abolished the in vitro synthesis of [(3)H]norepinephrine from L-[(3)H]tyrosine in slices and in synaptosomes of the rat cortex. However, normal [(3)H]dopamine synthesis could still be observed in both cortical preparations from animals with lesions. These results provide the first biochemical support for the existence of dopaminergic terminals independent of noradrenergic terminals in the rat cortex.
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The effects of intracerebral injections of 6-OHDA on self-stimulation were examined. Small amounts of 6-OHDA were injected either in the area ventralis tegmenti (AVT) or laterally in the pedonculus cerebellaris superior (PCS), then all rats were implanted in the AVT. In spite of marked depletion of brain catecholamines, self-stimulation learning was not altered by PCS 6-OHDA injections, whereas, AVT 6-OHDA injections produced a small perturbance. The administration of low doses of AMPT which had no observable effect in control rats, produced a severe depression of self-stimulation rates in 6-OHDA pretreated rats. The depressive effect of AMPT is always more important in rats injected with 6-OHDA in the AVT than those injected at the level of PCS. The respective role of noradrenergic and dopaminergic neurons in AVT self-stimulation are discussed.
The purpose of the present study was to systematically investigate the effects of the mammalian neuropeptide Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF) on nociception, using the tail-flick test. We report that ICV administration of NPFF induces a rapid and short-lasting hyperesthesic effect during day or night, for doses ranging from 10 ng to 10 micrograms. During the night, this hyperesthesic effect is followed by a long-lasting analgesic effect, the magnitude of which is related to the magnitude of the hyperesthesic effect. In addition to this intrinsic effect of NPFF, we report that NPFF reverses morphine-induced analgesia and that the magnitude of the response elicited by NPFF increases as a function of morphine-induced analgesia.
One hypothetical model for a mechanism of drug dependence involves the development of an adaptive process that is initiated to counter the acute effects of the drug. This adaptive process persists after the drug has been cleared from the brain, leaving an opposing reaction unopposed (abstinence signs). From a motivational perspective a particularly attractive hypothesis has been that of opponent process theory (32). Here many reinforcers elicit positive affective and hedonic processes that are opposed by negative affective and hedonic processes. Thus the intense pleasure of the opiate drug "rush" or "high" would be opposed by aversive withdrawal symptoms. The present paper presents neurobiological evidence to support the opponent process concept and suggests neural circuitry that may be involved. The region of the nucleus accumbens in the forebrain of the rat has been shown to be a particularly sensitive substrate not only for the acute reinforcing properties of opiate drugs, but also for the response disruptive effects of opiate antagonists in opiate dependent rats. This region also appears to be particularly sensitive to the aversive stimulus effects of opiate antagonists using a place aversion measure in dependent rats. These results suggest that the region of the nucleus accumbens and its neural circuitry may be an important neural substrate for both the positive and negative motivational aspects of drug dependence.
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