Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A(2A) receptor knockout mice

Abstract

Background and purpose. Purinergic system through the A2A adenosine receptor regulates addiction induced by different drugs of abuse. The aim of the present study was to investigate the specific role of A2A adenosine receptors in behavioral and neurochemical morphine responses related to its addictive properties. Experimental approach. Mice lacking A2A adenosine receptors and wild type littermates were used to evaluate behavioral responses induced by morphine. Antinociception was assessed using the tail-immersion and the hot-plate tests. Place conditioning paradigms were used to evaluate the rewarding effects of morphine and the dysphoric responses of morphine withdrawal. Microdialysis studies were carried out to evaluate changes in the extracellular levels of dopamine in the nucleus accumbens of A2A knockout mice after morphine administration. Key results. The acute administration of morphine induced a similar enhancement of locomotor activity and antinociceptive responses in both genotypes. However, the rewarding effects induced by morphine were completely blocked in A2A knockout mice. Besides, naloxone did not induce place aversion in animals lacking the A2A adenosine receptors. Conclusions and implications. Our findings demonstrate the relevant role played by A2A adenosine receptors in the addictive properties of morphine. Both, rewarding and aversive effects associated to abstinence were abolished in A2A knockout mice, supporting a differential role of the A2A adenosine receptor in somatic and motivational effects of morphine addiction. This study provides evidence about the role of A2A adenosine receptor as a general modulator of the addictive phenomenon.

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