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 depletion, a putative neurochemical correlate of the dysphoric symptomatology, are not yet understood. To assess the role of L-type calcium channels in the inhibition of the dopaminergic system in the withdrawal state, the effects of the dihydropyridine calcium channel antagonist nimodipine on the extracellular levels of dopamine were studied in the nucleus accumbens shell of awake rats 10 h after withdrawal from chronic ethanol intoxication. In control, chronic sucrose-withdrawn rats, nimodipine did not change extracellular dopamine levels. However, in ethanol-withdrawn rats nimodipine (5 or 10 mg/kg s.c.) increased extracellular dopamine to 136 +/- 16 and 305 +/- 19% of pre-administration values, respectively, the latter dose elevating levels above 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 behavioural items. Significant reductions of the score for convulsions (-47%) and, to a lesser extent, for catatonia (-30%) and tremors (-15%) contributed to the overall effect. It is suggested that overactivity of L-type calcium channels is involved in the mechanisms of dopamine depletion as well as in certain behavioural/neurological signs associated with ethanol withdrawal. By restoring depleted dopamine levels, dihydropyridines might ameliorate the dysphoric symptoms of ethanol abstinence.
Rossetti
Z L
ZL
Department of Neuroscience and C.N.R. Centre for Neuropharmacology, University of Cagliari, Italy. rossetti@vaxcal.unica.it
Isola
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D
De Vry
J
J
Fadda
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D000437:Alcoholism / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D000431:Ethanol; D009553:Nimodipine; D004298:Dopamine