Muscarinic receptors of the neostriatum--their role in controlling operant behavior in dogs.

Abstract

Chronic experiments were performed on six dogs to study the effects of bilateral microinjections of muscarinic receptor agonists and blockers into the dorsal striatum on the performance of an operant defensive reflex consisting of maintenance of a specified posture and on the differentiation of stimuli. Microinjections of carbachol, a non-selective agonist of muscarinic receptors, were accompanied by increases in the tonic component of movements, inhibition of phasic movements, ordering of the postural rearrangement, and increases in the amplitudes of its components. Bilateral microinjections of the selective agonist oxotremorine into the neostriatum had significantly weaker effects on the amplitude of postural rearrangement, generally decreasing the amplitude. Although oxotremorine also increased the tonic component of the operant response, this effect was weaker than that seen with carbachol microinjections. In addition, oxotremorine, unlike carbachol increased the number of intersignal limb elevations. These data, along with data published in the literature, are used to suggest the hypothesis that the actions of oxotremorine are mediated not only via muscarinic M2 but also via M1 receptors in the neostriatum. Stronger changes in responses to differential stimuli were also obtained after microinjection of the non-selective agonist carbachol than after microinjection of oxotremorine, and the fact that changes in responses to differential stimuli were significantly greater than changes in those to defensive stimuli suggests that microinjections of muscarinic M1 and M4 receptor agonists into the striatum are also accompanied by improvements in attention to significant stimuli.