Differential effects of M1 muscarinic receptor blockade and nicotinic receptor blockade in the dorsomedial striatum on response reversal learning

Abstract

The present studies determined whether blockade of M(1)-like muscarinic or nicotinic cholinergic receptors in the dorsomedial striatum affects acquisition or reversal learning of a response discrimination. Testing occurred in a modified cross-maze across two consecutive sessions. In the acquisition phase, a rat learned to turn to the left or to the right. In the reversal learning phase, a rat learned to turn in the opposite direction as required during acquisition. Experiment 1 investigated the effects of the M(1)-like muscarinic receptor antagonist, pirenzepine infused into the dorsomedial striatum on acquisition and reversal learning. Experiment 2 examined the effects of the nicotinic cholinergic antagonist, mecamylamine injected into the dorsomedial striatum on acquisition and reversal learning. Bilateral injections of pirenzepine at 10 microg, but not 1 microg, selectively impaired reversal learning. Analysis of the errors indicated that pirenzepine treatment did not impair the initial shift, but increased reversions back to the original response choice following the initial shift. Bilateral injections of mecamylamine, 6 or 18 microg, did not affect acquisition or reversal learning. The results suggest that activation of M(1) muscarinic cholinergic receptors, but not nicotinic cholinergic receptors, in the dorsomedial striatum is important for facilitating the flexible shifting of response patterns.

Fig. 1

Illustration of the cannula tip placements in the dorsomedial striatum for rats included in the behavioral analyses in Experiment 1. Cannula tips were concentrated in the dorsomedial striatal region ranging from −0.26 to 1.7 anterior to bregma. The number of circles does not match the total number of rats included in the behavioral analyses because certain cannula placements were overlapping to such a large extent that a single circle represents more than one cannula placement. Rat brain sections were modified from the atlas of Paxinos and Watson [26].

Fig. 2

(A) Mean trials to criterion on acquisition of the response discrimination after bilateral infusions of saline or pirenzepine (1 or 10 µg) into the dorsomedial striatum. The findings indicate that pirenzepine injections did not impair acquisition compared to that of saline infusions. The treatment received on this test is in bold for each group. SAL, saline; PRZ, pirenzepine. (B) Mean trials to criterion during reversal learning of the response discrimination after saline or pirenzepine infusions into the dorsomedial striatum. Pirenzepine infusions at the 10 µg dose, but not 1 µg dose, significantly increased the trials to criterion compared to that of saline injections (^*P < 0.05). The treatment received on this test is in bold for each group.

Fig. 3

(A) Mean number of perseverative errors during reversal learning of the response discrimination following saline or pirenzepine infusions. Pirenzepine infusions did not increase the number of perseverative errors compared to saline infusions. The treatment received on this test is in bold for each group. SAL, saline; PRZ, pirenzepine. (B) Mean number of regressive errors in reversal learning following saline or pirenzepine infusions. Infusion of pirenzepine (10 µg) significantly increased regressive errors compared to that of saline infusions and pirenzepine (1 µg) infusion (^*P < 0.05). The treatment received on this test is in bold for each group.

Fig. 4

Illustration of the cannula tip placements in the dorsomedial striatum for rats included in the behavioral analyses in Experiment 2. Cannula tips were concentrated in the dorsomedial striatal region ranging from −0.26 to 1.7 anterior to bregma. The number of circles does not match the total number of rats included in the behavioral analyses because certain cannula placements were overlapping to such a large extent that a single circle represents more than one cannula placement. Rat brain sections were modified from the atlas of Paxinos and Watson [26].

Fig. 5

(A) Mean trials to criterion on acquisition of the response discrimination after bilateral infusions of saline or mecamylamine (6 or 18 µg) into the dorsomedial striatum. The findings indicate that mecamylamine injections at either dose did not impair acquisition compared to that of saline infusions. The treatment received on this test is in bold for each group. SAL, saline; MEC, mecamylamine. (B) Mean trials to criterion during reversal learning of the response discrimination after saline or mecamylamine infusions into the dorsomedial striatum. Mecamylamine infusions at either dose did not affect trials to criterion on reversal learning. The treatment received on this test is in bold for each group.