Abstract
The effect of repeated administration of cocaine on presynaptic D 2 autoreceptor sensitivity in synaptosomes was studied. In rats treated chronically with saline, the dopamine D 2 agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) caused a significant inhibition of the Ca 2+-evoked 3H-DA release from synaptosomes prepared from the nucleus accumbens and from the striatum; this effect was blocked by the D 2 antagonist sulpiride. However, chronic cocaine pretreatment abolished the effect of N-0437 in both areas, suggesting a subsensitivity of release-modulating terminal DA autoreceptors. Subsensitive DA autoreceptors would enhance stimulated DA release from mesolimbic and nigrostriatal terminals and may play a role in the behavioral sensitization observed in this paradigm.
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