Relationship between alexithymia and dopamine D2-type receptor availability: Methamphetamine-dependent subjects differ from healthy controls

Abstract

Aims: Repeated cocaine administration produces perturbations in dopamine and glutamate neurotransmission that contribute to the reinstatement of extinguished cocaine seeking. Postsynaptic adenosine A2A receptors co-localize with dopamine D2 receptors in nucleus accumbens neurons, while presynaptic adenosine A2A receptors co-localize with adenosine A1 receptors on glutamate terminals. The synaptic localizationof adenosineA2A receptors represent targets for altering the dopamine and glutamate systems to effect the expression of behaviors associatedwith relapse. The goal of these studieswas to determine the effects of presynaptic or postsynaptic adenosine A2A receptor antagonism on the reinstatement of cocaine seeking. Methods:Male Sprague-Dawley rats self-administered cocaine in 10 daily self-administration sessions on a fixed-ratio 1 schedule. Lever pressing was extinguished in 6 daily extinction sessions. We first tested whether presynaptic and postsynaptic A2A receptor antagonism (SCH 442416 and KW 6002, respectively) was sufficient to reinstate cocaine seeking. We next tested the effects of SCH442416 and KW 6002 on reinstatement to cocaine seeking induced by cocaine. Results: Administration of the postsynaptic adenosine A2A receptor antagonist dose-dependently reinstated cocaine seeking and facilitated reinstatement induced by 5mg/kg cocaine, a dose that was alone insufficient to reinstate cocaine seeking. Administration of the presynaptic adenosine A2A receptor antagonist did not induce cocaine seekingwhen administered alone, but impaired cocaine-induced reinstatement induced by 15mg/kg cocaine. Conclusions: These findings highlight the importance of synaptic locations of adenosine A2A receptors in regulating cocaine seeking. Thus, antagonism of postsynaptic A2A receptors facilitates cocaine seeking, perhaps by enabling D2 receptor signaling. Antagonism of presynaptic A2A receptors, on the other hand, impairs cocaine seeking, perhaps by enabling adenosine A1 receptor activation and inhibition of glutamate transmission. Financial support: DA033358, DA029420, and CU Innovative Seed Grant.