Andrea T Alleweireldt1, Kenneth F Kirschner1, Camille B Blake1, Janet L Neisewander2. 1. Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA. 2. Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA. janet.neisewander@asu.edu.
Abstract
RATIONALE: Dopamine D1-receptor antagonists and agonists both attenuate cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains unclear whether these effects are D1-receptor mediated. OBJECTIVES: The present study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether behavioral disruption is involved in these effects. METHODS: Rats trained to press a lever for cocaine reinforcement with light and tone cues paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus complex was available). After responding diminished, the effects of the D1 antagonist on the dose-response functions of the D1 agonist for reinstatement of cocaine-seeking behavior by response-contingent cue presentations or cocaine priming were examined. A separate experiment assessed the effects of the agonist on the dose-response function of the antagonist for cue reinstatement. Stereotyped behavior and activity were also measured during each test session. RESULTS: The attenuating effects of SKF-81297 on cocaine-seeking behavior during cocaine-primed reinstatement were reversed by co-administration of SCH-23390. However, no evidence for reversal of the attenuation during cue reinstatement was found even though agonist-induced stereotypy and antagonist-induced hypoactivity were reversed by co-administration of the two drugs during the same test session. CONCLUSIONS: The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.
RATIONALE: Dopamine D1-receptor antagonists and agonists both attenuate cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains unclear whether these effects are D1-receptor mediated. OBJECTIVES: The present study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether behavioral disruption is involved in these effects. METHODS:Rats trained to press a lever for cocaine reinforcement with light and tone cues paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus complex was available). After responding diminished, the effects of the D1 antagonist on the dose-response functions of the D1 agonist for reinstatement of cocaine-seeking behavior by response-contingent cue presentations or cocaine priming were examined. A separate experiment assessed the effects of the agonist on the dose-response function of the antagonist for cue reinstatement. Stereotyped behavior and activity were also measured during each test session. RESULTS: The attenuating effects of SKF-81297 on cocaine-seeking behavior during cocaine-primed reinstatement were reversed by co-administration of SCH-23390. However, no evidence for reversal of the attenuation during cue reinstatement was found even though agonist-induced stereotypy and antagonist-induced hypoactivity were reversed by co-administration of the two drugs during the same test session. CONCLUSIONS: The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.
Authors: Kathleen M Kantak; Yolanda Black; Eric Valencia; Kristen Green-Jordan; Howard B Eichenbaum Journal: J Neurosci Date: 2002-02-01 Impact factor: 6.167
Authors: Callum Hicks; Peng Huang; Linnet Ramos; Sunil U Nayak; Yohanka Caro; Allen B Reitz; Garry R Smith; David Y-W Lee; Scott M Rawls; Lee-Yuan Liu-Chen Journal: ACS Chem Neurosci Date: 2018-04-06 Impact factor: 4.418