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Abstract :

Dopaminergic neurotransmission in the nucleus accumbens is generally thought to mediate the reinforcing properties of psychostimulant drugs, such as cocaine.
However, recent studies have suggested that distinct behavioral aspects of cocaine self-administration rely on a variety of striatal subregions, not restricted to the nucleus accumbens. For example, it has been shown that the most ventromedial part of the striatum, including the nucleus accumbens shell and the olfactory tubercle, is important for the acquisition of cocaine self-administration1. The dorsolateral striatum, in turn, has been associated with the well-established or perhaps habitual aspects of cue-controlled cocaine seeking2-4. Here, we examined the involvement of dopamine receptors in different areas of the striatum in early stages of cocaine self-administration. We hypothesized that in animals with limited drug experience, the ventral part of the striatum plays a more prominent role in cocaine self-administration than the dorsal striatum, which becomes involved with increasing drug experience. Rats were trained to self-administer cocaine (0.25 mg/inf) on a Fixed Ratio-1 schedule of reinforcement. After responding had stabilized, rats were infused with different doses of the dopamine receptor antagonist, α-flupenthixol, in one of the following regions of the striatum: dorsolateral striatum, dorsomedial striatum, nucleus accumbens core and nucleus accumbens shell. Somewhat unexpectedly, the data suggest that in both the ventral and the dorsal striatum, dopamine receptor stimulation plays an important, but distinct, role in cocaine self-administration in animals with limited cocaine experience.

Jean Pierre Konsman Unité Françoise Moos