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The Journal of Neuroscience, June 1, 1999, 19(11):4674 4681 Relationships between the Prefrontal Cortex and the Basal Ganglia in the Rat: Physiology of the Cortico-Nigral Circuits Nicolas Maurice,1

Pasteur, Rue Fiber, 75005 Paris CEDEX 04, France. Abstract Objectives: The aim of this paper is to summarize recent brain imaging research on the cortico-subcortico-basal ganglia (CNS, including both the signal and bilateral cortices). To this end, a number of hypotheses based on the results of the study of Née let al. have been examined, using a review of recent findings regarding the mechanisms of action of amphetamine and related psychostimulants to affect different functions of the basal ganglia in different brain regions of the rat. Results: Although the main objectives of the paper have been accomplished, there is still much to learn about the mechanisms of action of amphetamine and related psychostimulant drugs on the CNS. Keywords: amphetamine, psychostimulant, rat, basal ganglia, cerebral cortex, nucleus incumbent Introduction Amphetamine and related psychostimulants are psychostimulant drugs that activate central norepinephrine and dopamine uptake systems and affect several neurotransmitter systems involved in the functions of the basal ganglia. In animals, the brain-stimulating effects of cocaine may be attributed to its capacity to increase the release of norepinephrine and dopamine from the dorsal and medial prefrontal cortex (1,2). In humans, the dopaminergic actions of psychostimulants are less well characterized. Amphetamine (5,6-methylenedioxyamphetamine) is known to inhibit glutamate uptake in the prefrontal cortex and in the substantia nigra pars compact but not in the pallidum, and this effect is more robust with lower doses of amphetamine (reviewed in ref. 3). Amphetamine also increases the release of glutamate in the cortex and dent ate gyrus (4,5,6), and this effect is particularly striking at doses lower than those reported producing the stimulant effects of cocaine or amphetamine (3,5,8,9). However, the specific effects of amphetamine on glutamate release are not known. Furthermore, the specific neuronal effects of amphetamine on the basal ganglia, the nigrostriatal-striatal circuits involved in a number of behavioral functions, including motor learning, spatial learning, and emotional learning, remain obscure (2,5,8).

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