Operant behavior in conditions of activation and blockade of neostriatal muscarinic receptors.

Chronic experiments were performed on four dogs using a model of an operant defensive reflex associated with maintaining a flexion posture to study the effects of bilateral intraneostriatal microinjection of the non-selective muscarinic receptor agonist carbachol, the selective D2 dopamine receptor blocker raclopride, and the selective M1 muscarinic receptor blocker pirenzipine on the performance of the operant defensive reflex and differentiation of signals. The results show that microinjection of carbachol induced increases in the tonic component and inhibition of the phasic component of the reflex, an ordering rearrangement of the posture, and increases in the amplitudes of its components. Raclopride microinjection gave similar but less marked results. The greatest effects with both substances were seen using differential stimuli. There were sharp increases in the process of differentiation of sound signals. Pirenzipine microinjections gave the opposite result. These data are assessed on the basis of concepts of the existence of two efferent outputs from the neostriatum with opposite effects on their targets and the roles of muscarinic and dopamine receptors in triggering and blocking these effects.

Effects of the cholinergic system of the rat neostriatum on learning active escape in normal animals and in animals with lesions to the intralaminar thalamic nuclei.

Studies were carried out into the role of the parafascicular (Pf) nuclei of the rat thalamus in learning a conditioned active escape reflex (CAER) in a T-maze, a reflex associated with discrimination of visual stimuli, and into the regulatory effect on this learning process of activation of the neostriatal cholinergic system. The following results were obtained using 57 Sprague-Dawley rats divided into a number of experimental groups: 1) bilateral microinjection of carbacholine (0.03 microgram) into the neostriatum on days 4, 5, and 6 of training produced significant (p < 0.01) increases in the proportion of correct discriminant CAER performances; 2) bilateral lesioning of the Pf nuclei led to irreversible disruption of the previously learned CAER. Rats with initially bilaterally lesioned Pf nuclei did not learn the discriminant CAER at all after 10 days of training (16 combinations), and microinjection of carbacholine into the neostriatum of these animals was ineffective. It is concluded that the integrity of the afferent input into the Pf nuclei of the thalamus is an important factor for activation of the neuronal background of the neostriatum, and is required for cholinergic activation of the neostriatum to be effective.

Effects of microinjection of scopolamine into the neostriatum of rats on performance of a food conditioned reflex at different levels of fixation.

Chronic experiments performed on 32 Sprague-Dawley rats using a movement-feeding operant reflex (Skinner box) model showed that microinjection of scopolamine into the neostriatum had effects on this reflex which depended on the stage of learning. In animals with weakly fixed reflexes (prior to reaching the stage of memory consolidation), bilateral microinjection of 0.3 microgram of scopolamine into the caudate nucleus completely inhibited the reflex for a prolonged period of time. When the operant habit was well fixed, bilateral microinjection of the same doses of scopolamine into the neostriatum had no effect on the reflex. These results suggest that the neostriatum cholinergic system is critically involved in forming the motor engram. The cholinergic system of the caudate nucleus either takes no part in realizing the well-fixed conditioned reflex movement response and/or other forebrain structures are involved in the reflex, compensating for the disturbance in neostriatal cholinergic function.

Role of the cholinergic system of the neostriatum in regulating several forms of defensive behavior.

Studies were carried out on the effects of microinjection of carbacholine, a choline receptor agonist, into the dorsal striatum on the discrimination of sensory signals in chronic experiments on dogs with an operant defensive reflex involving maintenance of a flexor pose and in rats trained to a conditioned active escape reflex (CAER) in a T-maze; the sensory signals involved were important in the behavioral situations used. Carbacholine microinjection improved the process of discrimination, with an increase in the number of correct responses in rats in the T-maze discrimination-requiring CAER, and with improvements in responses to differentiation stimuli in the operant defensive reflex requiring maintenance of a defined pose in dogs. The efficiency of the effect depended on the level of training. There were two situations in which responses did not improve: when there was no signal discrimination in background conditions before microinjection, and in conditions of complete differentiation of the signals, i.e., complete training. It would appear that the neostriatum is not involved in the behavioral reactions in either of these situations, and this may result primarily from low levels of neuronal activity in response to these signals.