Motor and cognitive functions of the neostriatum during bilateral blockade of its dopamine receptors.

Studies on 60 Sprague-Dawley rats were performed to compare systemic and intrastriate administration of the selective D1 dopamine receptor blocker SCH23390 on the acquisition of a discriminant conditioned active avoidance reflex (CAAR) in a T maze and on behavior in an open field test. Systemic treatment at a dose of 0.025 mg/kg produced several-fold reductions in the proportion of correct performances of the discriminant CAAR and motor activity in the open field test. At the same time, bilateral microinjection of SCH23390 into the rat neostriatum at doses of 0.004-1.0 microg did not induce any deterioration in learning of the discriminant CAAR as compared with intact controls, though there was a sharp inhibition of motor activity in the open field test. Bilateral microinjections of the D2 dopamine receptor blocker raclopride into the rat neostriatum at a dose of 0.004 microg produced a marked and long-lasting degradation of learning of the discriminant CAAR. These data lead to the following conclusions: 1) the differences in the effects of systemic and intrastriate administration of SCH23390 appear to be associated with the fact that the behavioral changes seen after systemic administration may be mediated mainly by structures differing from neostriatal D1 receptors, and 2) the D1-mediated effects of the nigrostriatal dopaminergic system on the neostriatum are complex, with activation of motor activity (projection spiny neurons of the direct pathway) and weak modulation of the learning process (large aspiny cholinergic interneurons). Modulation of the learning process evidently occurs via neostriatal D2 dopaminergic receptors.