Elsevier

Neuroscience

Volume 179, 14 April 2011, Pages 143-150
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Quinpirole-induced sensitization to noisy/sparse periodic input: temporal synchronization as a component of obsessive-compulsive disorder

https://doi.org/10.1016/j.neuroscience.2011.01.048Get rights and content

Abstract

Quinpirole-sensitized rats were tested on a discrete-trials 40-s peak-interval procedure using lever pressing as the instrumental response. Although there was no evidence of rhythmical activity in lever pressing, periodic output was observed in a secondary response (food-cup entries) during the inter-trial interval following the delivery of reinforcement on fixed-interval trials, but not during unreinforced probe trials. This repetitive pattern of behavior with a 40-s period points to the primacy of reinforcement as a time marker and an increased tendency to synchronize to noisy and sparse periodic input as a result of reduced inhibitory control in cortico-striatal circuits following chronic quinpirole administration. Parallels between quinpirole-induced rhythmical behavior and the repetitive motor habits frequently observed in obsessive-compulsive disorder are discussed.

Research highlights

▶Rats are studied using a 40-s peak-interval timing procedure. ▶We examine changes in timing as a function of quinpirole administration. ▶Quinpirole-induced rhythmical behavior similar to the repetitive motor habits frequently observed in obsessive-compulsive disorder. ▶Observations are discussed in terms of excitation and inhibition of cortical-striatal circuits.

Section snippets

Subjects

Ten Sprague-Dawley male rats (Charles River VAF plus) approximately 4-months of age were housed in pairs in a temperature-controlled room, under a 12-h light/dark (L/D) cycle. Rats were provided free access to water in their home cages and were maintained at 85% of their ad lib weights by restricting access to food (Rodent Diet 5001, PMI Nutrition International, Inc., Brentwood, MO, USA). Experiments were conducted during the light portion of the L/D cycle in accordance with standard procedures

Drug administration and behavioral testing

For control rats given saline injections, during FI trials both the rate of lever pressing and food-cup entries gradually increased as a function of signal duration up until the time of reinforcement at 40 s after which lever presses abruptly decreased and food-cup entries abruptly increased. Following a 10–20-s period of food-cup checking, both responses were emitted randomly and at a low level for the remainder of the ITI (160-s min). In contrast, on unreinforced probe trials, lever pressing

Discussion

The present results demonstrated an unexpected level of rhythmical behavior in a secondary measure of responding (e.g. food-cup entries) that is a necessary action for the retrieval of the reward (e.g. food pellet), but not the instrumental response required to produce its delivery. As a consequence, this behavior is typically not recorded or analyzed during most timing experiments in which lever pressing is the reinforced response. The fact that it is a “secondary” response, and arguably more

Conclusion

In summary, our proposal is that there is an increased tendency to entrain to noisy and sparse periodic input as a result of reduced inhibitory control in cortico-striatal circuits following chronic QNP administration or in OCD patients. As a consequence, the repetitive motor habits frequently observed in OCD will have a tendency to be synchronized to specific temporal regularities in the environment that would normally be inhibited (Meck and Benson, 2002, Swerdlow, 2001). Moreover, it has been

Acknowledgments

This research was supported, in part, by a fellowship from the National Science Council of Taiwan to WHM. The authors would like to thank E. Crawford for assistance in training the rats.

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