Effects of calcium channel blockade on intravenous self-administration of ethanol in rats

In the present study the involvement of voltage-operated calcium channels ( VOCCs) in the acquisition and maintenance of operant i.v. ethanol (EtOH) se lf-administration was investigated in rats. Rats readily learned to self-ad minister EtOH (unit dose range: 0.5-4% v/v) within five daily 2-h sessions, when infusions were made contingent upon nose-poking in a hole containing infrared sensors. Response rate was related to the EtOH concentration in an inverted U-shaped manner, the maximal rate and intake being observed at a unit dose of 1% v/v (0.27 mg EtOH/infusion). Self-administration of EtOH ap peared to be behaviorally specific, as responding in the reinforced hole di d not coincide with increased responding in a nonreinforced hole. Daily tre atment with the dihydropyridine VOCC blocker nimodipine (2.5-20 mg/kg, i.p. , t-15 min) dose-dependently attenuated acquisition of EtOH self-administra tion; the 5 mg/kg dose resulting in a partial, and the 10 and 20 mg/kg dose s in a complete prevention of i.v. self-administration behavior. The effect s of nimodipine (2.5-5.0 mg/kg) were considered to be relatively specific, as an inhibition of the reinforced responding could be demonstrated in the absence of a significant effect on nonreinforced responding. When tested in rats showing stable self-administration behavior (unit dose: 1% v/v EtOH), nimodipine showed biphasic dose-response effects; with 2.5 and 5 mg/kg res ulting in a mild increase, and 10 and 20 mg/kg resulting in a decrease of s elf-administration behavior, respectively. The present study suggests that blockade of VOCCs attenuates the reinforcing stimulus effects of EtOH; and, as such, the data may offer an explanation for the previously reported EtO H intake-reducing effects of dihydropyridine calcium channel ligands obtain ed in two-bottle choice paradigms. Dihydropyridine derivatives, such as nim odipine, may therefore offer an interesting approach to the pharmacotherapy of alcoholism. (C) 1999 Published by Elsevier Science B.V./ECNP All rights reserved.