Effects of nimodipine on extracellular dopamine levels in the rat nucleus accumbens in ethanol withdrawal

Withdrawal from chronic ethanol intoxication is associated with a reduction of dopamine neurotransmission. However, the mechanisms of dopamine depleti on, a putative neurochemical correlate of the dysphoric symptomatology, are not yet understood. To assess the role of L-type calcium channels in the i nhibition of the dopaminergic system in the withdrawal state, the effects o f the dihydropyridine calcium channel antagonist nimodipine on the extracel lular levels of dopamine were studied in the nucleus accumbens shell of awa ke rats 10 h after withdrawal from chronic ethanol intoxication. In control , chronic sucrose-withdrawn rats, nimodipine did not change extracellular d opamine levels. However, in ethanol-withdrawn rats nimodipine (5 or 10 mg/k g s.c.) increased extracellular dopamine to 136 +/- 16 and 305 +/- 19% of p re-administration values, respectively, the latter dose elevating levels ab ove those of controls. The elevations of extracellular DA by nimodipine (10 mg/kg) were associated with a significant reduction (-17%) of the overall behavioural score of the withdrawal symptomatology, as evaluated for 11 beh avioural items. Significant reductions of the score for convulsions (-47%) and, to a lesser extent, for catatonia (-30%) and tremors (-15%) contribute d to the overall effect. It is suggested that overactivity of L-type calciu m channels is involved in the mechanisms of dopamine depletion as well as i n certain behavioural/neurological signs associated with ethanol withdrawal . By restoring depleted dopamine levels, dihydropyridines might ameliorate the dysphoric symptoms of ethanol abstinence. (C) 1999 Elsevier Science Ltd . All rights reserved.