Elsevier

Neuroscience

Volume 137, Issue 2, 2006, Pages 699-706
Neuroscience

Research paper
Systems neuroscience
Dopamine D1 or D2 receptor antagonism within the basolateral amygdala differentially alters the acquisition of cocaine-cue associations necessary for cue-induced reinstatement of cocaine-seeking

https://doi.org/10.1016/j.neuroscience.2005.08.064Get rights and content

Abstract

The basolateral amygdala complex has been implicated in the formation and utilization of cocaine-cue associations in rat models of cue-induced reinstatement to cocaine-seeking behavior. We have previously demonstrated the importance of dopamine inputs to the basolateral amygdala complex in the reinstatement of cocaine-seeking behavior following chronic cocaine self-administration. Here we show that selective blockade of amygdalar dopamine D1 and D2 receptors during acquisition of cocaine-cue associations has distinctive effects on subsequent conditioned-cued cocaine-seeking behavior. Male, Sprague–Dawley rats were first trained to self-administer i.v. cocaine on a fixed ratio 1 schedule for 5 days. Subjects then received bilateral, intra-basolateral amygdala complex infusions of a dopamine D1 receptor antagonist (SCH23390, 0.25–2.0μg/side; experiment 1), a dopamine D2 receptor antagonist (raclopride, 0.625–5.0μg/side; experiment 2), or vehicle just prior to a single classical conditioning session, during which a light+tone cue was discretely paired with passive infusions of cocaine in the absence of lever responding. Following five additional days of cocaine self-administration and 7–10 days of extinction training, animals underwent multiple tests for cue-induced reinstatement. SCH23390 (2.0μg/side), administered at the time of cocaine-cue association only, produced an attenuation of reinstatement to cue-induced cocaine-seeking behavior. In contrast, low doses of raclopride potentiated, while a higher dose of raclopride attenuated cue-induced reinstatement. These results demonstrate unique contributions of D1 vs. D2 receptors in mediating dopamine inputs within the basolateral amygdala complex during the formation of cocaine-stimulus associations that are critical for cue-induced reinstatement.

Section snippets

Subjects

Male Sprague–Dawley rats (Charles River, Wilmington, MA, USA), weighing 275–350g at the time of surgery, were housed individually on a reverse light/dark cycle. Rats were maintained on 20–25g of rat chow per day, with water available ad libitum. All protocols were approved by the Institutional Animal Care and Use Committee of the Medical University of South Carolina and carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (National

Histology

A schematic indicating the placement of the infusion cannulae tips of animals that received bilateral SCH23390, raclopride, or vehicle into the BLA is shown in Fig. 1. Subjects with cannulae tracts that did not meet the criteria of bilateral BLA placement are also included in the schematic and the data from these animals were used as an anatomical control group (histology outliers). These animals were fairly evenly distributed over all nine of the treatment groups (n=1–4) and the anatomical

Discussion

In the present study, we examined the role of BLA DA receptors in the formation of cocaine-cue associations in rats trained to self-administer i.v. cocaine and in the subsequent conditioned-cued reinstatement of cocaine-seeking behavior. DA D1 receptor blockade within the BLA during a single cocaine-cue pairing session attenuated the later expression of conditioned-cued reinstatement. DA D2 receptor blockade within the BLA prior to the cocaine-cue pairing session had unique dose-dependent

Acknowledgments

This research was supported by National Institute on Drug Abuse grant DA10462 (R.E.S.) and NIH grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources.

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