Ryan K Bachtell1, David W Self. 1. Department of Psychology and Neuroscience, University of Colorado, UCB 345, Boulder, CO 80309-0345, USA. Ryan.Bachtell@Colorado.edu
Abstract
RATIONALE: Dopamine (DA) receptor stimulation in the nucleus accumbens (NAc) plays an important role in regulating cocaine-seeking behavior. Adenosine receptors antagonize the effects of DA receptor stimulation on intracellular signaling, neuronal output, and behavior. OBJECTIVES: The goal of the present study is to determine the effects of adenosine A(2A) receptor stimulation on reinstatement of cocaine-seeking behavior in rats. METHODS: Rats were trained to lever press for cocaine in daily self-administration sessions on a fixed-ratio 1 schedule for 3 weeks. After 1 week of abstinence, lever pressing was extinguished in six daily extinction sessions. We subsequently assessed the effects of the adenosine A(2A) receptor agonist, CGS 21680, on cocaine-, quinpirole (D(2) agonist)-, and cue-induced reinstatement to cocaine seeking. We also assessed the effects of CGS 21680 on sucrose seeking in rats extinguished from sucrose self-administration. RESULTS: Pretreatment of CGS 21680 dose-dependently blunted cocaine-induced reinstatement (15 mg/kg, i.p.). Pretreatment with CGS 21680 (0.03 mg/kg, i.p.) also attenuated quinpirole- and cue-induced reinstatement. A minimally effective dose of CGS 21680 failed to alter cocaine-induced locomotor activity or sucrose seeking. CONCLUSIONS: Stimulation of adenosine A(2A) receptors antagonizes reinstatement of cocaine seeking elicited by cocaine, DA D(2)-receptor stimulation, and cocaine-conditioned cues. These findings suggest that adenosine A(2A) receptor stimulation may oppose DA D(2) receptor signaling in the NAc that mediates cocaine relapse.
RATIONALE: Dopamine (DA) receptor stimulation in the nucleus accumbens (NAc) plays an important role in regulating cocaine-seeking behavior. Adenosine receptors antagonize the effects of DA receptor stimulation on intracellular signaling, neuronal output, and behavior. OBJECTIVES: The goal of the present study is to determine the effects of adenosine A(2A) receptor stimulation on reinstatement of cocaine-seeking behavior in rats. METHODS:Rats were trained to lever press for cocaine in daily self-administration sessions on a fixed-ratio 1 schedule for 3 weeks. After 1 week of abstinence, lever pressing was extinguished in six daily extinction sessions. We subsequently assessed the effects of the adenosine A(2A) receptor agonist, CGS 21680, on cocaine-, quinpirole (D(2) agonist)-, and cue-induced reinstatement to cocaine seeking. We also assessed the effects of CGS 21680 on sucrose seeking in rats extinguished from sucrose self-administration. RESULTS: Pretreatment of CGS 21680 dose-dependently blunted cocaine-induced reinstatement (15 mg/kg, i.p.). Pretreatment with CGS 21680 (0.03 mg/kg, i.p.) also attenuated quinpirole- and cue-induced reinstatement. A minimally effective dose of CGS 21680 failed to alter cocaine-induced locomotor activity or sucrose seeking. CONCLUSIONS: Stimulation of adenosine A(2A) receptors antagonizes reinstatement of cocaine seeking elicited by cocaine, DA D(2)-receptor stimulation, and cocaine-conditioned cues. These findings suggest that adenosine A(2A) receptor stimulation may oppose DA D(2) receptor signaling in the NAc that mediates cocaine relapse.
Authors: Kjell Fuxe; Dasiel O Borroto-Escuela; Wilber Romero-Fernandez; Miklós Palkovits; Alexander O Tarakanov; Francisco Ciruela; Luigi F Agnati Journal: Neuropsychopharmacology Date: 2013-09-06 Impact factor: 7.853
Authors: Richard M Kostrzewa; Karolina Wydra; Malgorzata Filip; Cynthia A Crawford; Sanders A McDougall; Russell W Brown; Dasiel O Borroto-Escuela; Kjell Fuxe; Raul R Gainetdinov Journal: J Pharmacol Exp Ther Date: 2018-06-19 Impact factor: 4.030