Adenosinergic System: Therapeutics for Drug Addiction
Adenosinergic System: Therapeutics for Drug Addiction
The generation of transgenic rodents for investigating the clear cut role of the adenosinergic mechanism is quite challenging in the context of addiction behavior. Several laboratories have used knockout technologies to study the role of adenosine and its metabolizing enzymes such as adenosine kinase.
Apart from this, the development of specific adenosine A2A receptor knockout rodents would be a useful tool in discerning the interaction of striatal adenosine receptors with those of DA D2 receptors in the synaptic neurotransmissions involved in the addiction phenomenon. Adenosine A2A receptor gene deletion was shown to alter the behavioral effects produced by several addictive drugs in rodents, especially mice, and this has been demonstrated in the nicotine-induced conditioned place preference test in A2A knockout mice. Furthermore, the promising effect of these transgenic animals was also suggested by the report that showed that both the rewarding and aversive effects of Δ-tetrahydrocannabinol, a cannabinoid CB1 receptor agonist, were reduced, and the expression of rimonabant, a cannabinoid CB1 receptor antagonist-precipitated Δ-tetrahydrocannabinol withdrawal was also found to be attenuated in adenosine A2A receptor knockout mice. Adenosine was also shown to be involved in opioid dependence as the blockade of adenosine metabolism by adenosine kinase inhibitors decreases the severity of morphine withdrawal. However, the study of addiction phenomenon in the context of adenosine hyper- or hypo-function in the frontal cortical areas or the striatum involved in the addiction process, can accomplish better translational research results. The development of mice with overexpression of adenosine kinase in these areas could also give interesting results in the pathological mechanisms involved in the process of drug withdrawal syndrome.
Genetic Manipulations of Adenosine Signaling for Addiction Treatment
The generation of transgenic rodents for investigating the clear cut role of the adenosinergic mechanism is quite challenging in the context of addiction behavior. Several laboratories have used knockout technologies to study the role of adenosine and its metabolizing enzymes such as adenosine kinase.
Apart from this, the development of specific adenosine A2A receptor knockout rodents would be a useful tool in discerning the interaction of striatal adenosine receptors with those of DA D2 receptors in the synaptic neurotransmissions involved in the addiction phenomenon. Adenosine A2A receptor gene deletion was shown to alter the behavioral effects produced by several addictive drugs in rodents, especially mice, and this has been demonstrated in the nicotine-induced conditioned place preference test in A2A knockout mice. Furthermore, the promising effect of these transgenic animals was also suggested by the report that showed that both the rewarding and aversive effects of Δ-tetrahydrocannabinol, a cannabinoid CB1 receptor agonist, were reduced, and the expression of rimonabant, a cannabinoid CB1 receptor antagonist-precipitated Δ-tetrahydrocannabinol withdrawal was also found to be attenuated in adenosine A2A receptor knockout mice. Adenosine was also shown to be involved in opioid dependence as the blockade of adenosine metabolism by adenosine kinase inhibitors decreases the severity of morphine withdrawal. However, the study of addiction phenomenon in the context of adenosine hyper- or hypo-function in the frontal cortical areas or the striatum involved in the addiction process, can accomplish better translational research results. The development of mice with overexpression of adenosine kinase in these areas could also give interesting results in the pathological mechanisms involved in the process of drug withdrawal syndrome.
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