Time and sex-dependent effects of an adenosine A2A/A1 receptor antagonist on motivation to self-administer cocaine in rats.

Pharmacology, Biochemistry, and Behavior
Susan E DoyleWendy J Lynch

Abstract

Adenosine is an important neuromodulator, known to interact with both dopaminergic and glutamatergic systems to influence psychostimulant action. In the present study, we examined the effects of ATL444, a novel adenosine receptor antagonist, on motivation for cocaine in male and female rats. Adult male and female Sprague-Dawley rats were trained to self-administer cocaine (1.5mg/kg/infusion) on a fixed-ratio 1 schedule with a daily maximum of 20 infusions. Following 5 consecutive sessions during which all 20 available infusions were obtained, motivation for cocaine (0.5 mg/kg/infusion) was assessed under a progressive ratio (PR) schedule, and once responding stabilized, the effect of treatment with ATL444 (0, 15, and 30 mg/kg, i.p.) was examined. As a control, we also assessed its effects on PR responding for sucrose. Binding studies revealed that ATL 444 was 3-fold, 25-fold, and 400-fold more selective for the A2A receptor as compared to A1, A2B, and A3 receptors, respectively. ATL444 produced a significant increase in motivation for cocaine on the day of treatment in females with a trend for an increase in males. In addition, over the two PR sessions following ATL444 treatment a significant decrease in responding was observed...Continue Reading

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Citations

Mar 14, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Carolina P RamôaWendy J Lynch
Jan 30, 2018·Frontiers in Pharmacology·Inmaculada Ballesteros-YáñezStefania Gessi
Nov 6, 2018·Psychopharmacology·Nicholas S HaynesRyan K Bachtell
Feb 11, 2020·Journal of Neurochemistry·Jason R BorgusB Jill Venton
Aug 16, 2019·European Journal of Nuclear Medicine and Molecular Imaging·Athanasios KatsikisMaria Koutelou
Jun 23, 2018·Frontiers in Physiology·Andrea PorzionatoRaffaele De Caro

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