Role of dopamine D3 receptors in the expression of conditioned fear in rats.

Abstract

There has been considerable interest in the role of dopamine D(3) receptors in appetitive conditioning but few studies have examined their role in aversive conditioning. The present study examined the effect of the dopamine D(3) receptor-preferring partial agonist BP 897 (1-(4-(2-naphthoyl-amino)butyl)-4-(2-methoxyhenyl)-1A-piperazine hydrochloride) and the selective dopamine D(3) receptor antagonist SB-277011A (trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]syclohexyl]4-quinolininecarboxamide]) on the expression and acquisition of fear conditioning. Rats (N=143) received 3 conditioned stimulus-shock pairings and then received 15 conditioned stimulus-alone presentations (3 per day) while lever pressing for food. Response suppression was taken as the behavioral measure of fear. Rats showed strong suppression to the conditioned stimulus after it had been paired with shock and suppression progressively weakened over conditioned stimulus-alone presentations. In experiment 1, rats that received BP 897 (1.0, 2.0 mg/kg i.p.) or SB-277011A (10.0 mg/kg i.p.) prior to conditioned stimulus-alone presentation sessions showed reduced suppression to the conditioned stimulus as compared to rats that received vehicle or lower doses of drug (0, 0.1 mg/kg BP 897; 0, 0.5, 5.0 mg/kg SB-277011A). Injections of BP 897 (1.0, 2.0 mg/kg) or SB-277011A (10.0 mg/kg) prior to conditioned stimulus-shock pairings did not significantly affect subsequent response suppression. Thus, BP 897 and SB-277011A dose-dependently attenuated the expression but not the acquisition of conditioned fear. These findings suggest that BP 897 and SB-277011A reduce the control of responding by aversively conditioned stimuli.

• Authors: Shelley N Swain, Jonathan Beuk, Christian A Heidbreder, Richard J Beninger
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 579 Issue 1-3 Pg. 167-76 (Jan 28 2008) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17996231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitriles
• Piperazines
• Receptors, Dopamine D3
• SB 277011
• Tetrahydroisoquinolines
• BP 897

Topics

• Animals
• Avoidance Learning (drug effects, physiology)
• Behavior, Animal (drug effects, physiology)
• Dose-Response Relationship, Drug
• Electroshock
• Fear (drug effects, physiology)
• Male
• Nitriles (administration & dosage, pharmacology)
• Piperazines (administration & dosage, pharmacology)
• Rats
• Rats, Wistar
• Receptors, Dopamine D3 (antagonists & inhibitors, metabolism)
• Tetrahydroisoquinolines (administration & dosage, pharmacology)