Article
Involvement of Striatal Cholinergic Receptors in Reaction Time and Fixed-Interval Responding in Rats

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Abstract

In the present study the effects of intrastriatal scopolamine injections (0, 3, and 10 μg) were evaluated in two operant tasks. The first task tested the reaction time performance of rats, while the other task measured responding in a temporal discrimination test (fixed-interval 30 s). In the reaction time task, in which the rats had to hold down a lever during a variable interval, blockade of striatal muscarinic receptors resulted in a decrease in the total number of trials that the rats completed. Scopolamine also decreased the proportion of anticipatory responses, i.e., premature releases of the lever. The reaction time was not affected after scopolamine infusions. In the temporal discrimination task, the number of emitted responses was decreased after scopolamine infusions. However, the number of trials completed in the fixed interval task was not affected by scopolamine. It was concluded that the striatal cholinergic neurons are involved in organization of motor responses.

Introduction

The striatum plays a pivotal role in the organization and execution of motor programs and in aspects of cognitive functions 10, 21. The control of motor behavior by the striatum involves different neurotransmitter systems, for example, dopamine, glutamate, and GABA. The main focus in this field has been directed towards the dopaminergic system because this neurotransmitter is severely affected in Parkinson’s disease. More recently, interest has been going out to the interactions between the dopaminergic, glutamatergic, and GABAergic neurotransmission in the control of movement 4, 15.

Within the striatum there is a dense distribution of cholinergic neurons that predominantly have projections within the striatum. Several studies have shown that striatal acetylcholine can be modulated by the dopaminergic system 11, 12, 13. There is anatomical evidence that suggests that muscarinic receptors are colocalized with dopamine receptors [7], which could indicate that acetylcholine and dopamine intimately linked in striatal functions. The finding that a cholinergic antagonist ameliorated haloperidol-induced impairment in reaction time responding [8], demonstrates that there is a close relation between striatal acetylcholine and dopamine. Further evidence for an interaction between the cholinergic and dopaminergic system comes from a study that reported a concomitant decrease in the expression of muscarinic and dopaminergic (type 2) receptors after circling training [16]. A recent study also indicated that the striatal muscarinic receptors modulate the level of dopamine, glutamate, and GABA in the striatum [23]. These data support the notion that the striatal cholinergic interneurons could have a prominent role in the control of motor behavior [13].

Although the above data may indicate that direct modulation of the striatal cholinergic neurons could affect motor behavior, data on the functional consequences of striatal muscarinic blockade are scarce (e.g., [25]). The present study was a first attempt to evaluate the behavioral consequences of blockade of the striatal muscarinic receptors in operant responding in rats. The effects of intrastriatal infusions of scopolamine were examined in a reaction time task [2]and a temporal discrimination task. Both tests examined whether the direct blockade of the striatal cholinergic receptors affected operant responding in rats.

Section snippets

Subjects

The present study was approved by the local ethical committee of the University of Maastricht. Eight male Lewis rats (250–300 g at the start of the experiments) were used. After the rats were trained to perform the reaction time task (see below), the rats were anaesthetized with a combination of Ketamine (50 mg/kg, IM) and Rompun (4 mg/kg, SC) and placed in a stereotaxic frame. Stainless steel cannulae (outer diameter: 0.5 mm) were bilaterally implanted with the tip of the cannulae at the

Reaction Time

An overview of the results from the reaction time task is depicted in Fig. 1, Fig. 2. The number of trials that the rats completed decreased after administration of scopolamine [dose: F(2, 14) = 33.94, p < 0.01; see Fig. 1A]. The proportion of anticipatory responses decreased after infusion of the highest dose of scopolamine [dose: F(2, 14) = 5.16, p < 0.05; see Fig. 1B]. During vehicle sessions the rats made about 30 anticipatory responses, which means that rats made less than 0.4 of these

Discussion

The two tasks that were used in this study clearly showed that blockade of the striatal muscarinic receptors affected operant responding in the rat. In the reaction time task the number of anticipatory responses decreased after scopolamine administration. Also, after scopolamine infusions the number of trials that the rats completed was halved when compared with the performance in vehicle sessions. Although there was a tendency for an increase in the mean reaction time, two other analyses

Acknowledgements

I thank Wiel Honig for the technical assistance, and Huub Hamers for the technical development of the Skinner boxes. I am grateful to Dr. Fren Smulders for helping me with analyzing the reaction time distributions. My research has been made possible by a fellowship of the Royal Netherlands Academy of Arts and Sciences.

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