Receptor subtype-specific dopaminergic agents and unconditioned behavior.

Abstract

When all of the data concerning the role of D1 and D2 receptors in the control of unconditioned behaviors are taken together a fairly consistent picture begins to emerge. Considering first the normosensitive animals, it appears that D1 and D2 receptors are interdependent in their involvement in the control of locomotor activity. Stimulation of either receptor subtype leads to increases in activity although D2 agonists generally have a larger effect on activity than D1 agonists. Subeffective doses of D1 and D2 agonists (or D1 and D2 antagonists) have a synergistic action when co-administered. Injections of antagonists specific for either receptor subtype leads to a decrease in unstimulated locomotor activity or a diminution in the effects of agonists stimulating either receptor subtype. Besides locomotor activity, stimulation of D2 receptors produces yawning but a consistent effect on grooming has not been seen; D2 receptor stimulation also produces stereotyped behaviors. Again, there seems to be an interdependence between the two receptor subtypes; yawning or stereotypy produced by D2 receptor stimulation is blocked by either D2 or D1 antagonists. Stimulation of D1 receptors produces grooming and small perioral movements but not stereotyped behaviors like those typically seen following large doses of D2 agonists or DA agonists not specific a receptor subtype. Unlike D1 receptor-stimulated locomotor activity which is antagonized by D2 receptor blockers, grooming and perioral movements are not (but see Ref. 81). Thus, D1 receptor-mediated grooming and perioral movements seem to be exceptions to the otherwise general finding that co-stimulation of the two receptor subtypes needed for the expression of D1 or D2 agonist effects in normosensitive rats and mice. The apparent need to stimulate both D1 and D2 receptors to produce locomotor and some other unconditioned behaviors in normosensitive animals is lost in chronically denervated animals that are supersensitive to the effects of DA or DA agonists. However, there appear to be important species differences. Generally, in rodents undergoing unilateral or bilateral 6-OHDA-induced destruction of the nigrostriatal DA system, the locomotor effects of D1 agonists are not blocked by D2 antagonists and those of D2 agonists are not blocked by D1 antagonists. Similar results have been reported following chronic treatments with catecholamine depleting drugs. Thus, stimulation of either D1 or D2 receptors alone in DA supersensitive rodents appears to be sufficient to produce locomotor activity. In primates made DA supersensitive either with MPTP or as a result of Parkinson's disease, on the other hand, D2 but not D1 agonists are effective in reversing locomotor deficits.(ABSTRACT TRUNCATED AT 400 WORDS)