Comparison of the Effects of Systemic (intramuscular) and Intrastriatal Administration of a Selective D1 Dopamine Receptor Blocker on Motor Behavior and Postural Rearrangement in Dogs

Abstract

The present study was based on the concept (Shapovalova, 2000) that activation and blockade of different types of muscarinic and dopamine receptors located in different efferent outputs of the neostriatum should have different effects on motor behavior. The aim of the study was to compare the effects of systemic and intrastriatal injections of a selective D(1) dopamine receptor blocker on motor behavior. Experiments were performed on five dogs using a model of an operant defensive reflex associated with maintaining a defined flexor posture. The experiments, with recording, storage, and analysis of data, were performed using an original personal computer program. Systemic (intramuscular) administration of the D(1) dopamine receptor blocker SCH23390 at a dose of 0.025 mg/kg led to a sharp reduction in the amplitude of the operant defensive reflex, with complete refusal to perform it in most cases. The phasic component of the operant response showed the most significant level of inhibition, though the diagonal pattern of the postural rearrangement persisted. Bilateral microinjections of the same D(1) receptor blocker into the neostriatum at doses of 0.1 and 1.0 microg did not alter the proportion of correct solutions of the operant task, though the microinjections did induce a series of changes in motor activity, with significant increases in the latent period of the response, and in some cases increases in response amplitude, decreased phasicity, and complete cessation of intersignal raisings of the limb. These data lead to the following conclusions: 1) the difference in the effects of systemic and intrastriatal administration of SCH23390 evidently results from the fact that systemic administration can also block D(1) receptors in other structures in addition to the neostriatum; 2) the effects of the nigrostriatal dopaminergic system on the neostriatum mediated by D(1) receptors are complex, with activation of motor activity (projection spiny neurons in the direct pathway) and weak modulation of mental processes (large aspiny cholinergic interneurons); 3) regulation of movement and postural rearrangement is mediated by different efferent outputs of the neostriatum.