Adaptive changes in numbers of calcium channels in drug dependence.

Adrenal-derived cells in culture slowly upregulate numbers of putative calcium channel proteins in response to inhibitory drugs including ethanol, benzodiazepines and morphine. This appears to be an adaptive response to cell inhibition involving second messengers and protein phosphorylation and culminating in alterations in expression of the calcium channel gene (Fig. 1). These increases in calcium channels lead to rebound increases in cell excitability when the depressant drugs are withdrawn (a characteristic feature of chemical dependence on depressant drugs) so that this change in numbers of calcium channels may provide a model for one mechanism of chemical dependence. Similar findings have been reported in the brains of animals made dependent on depressant drugs, and genetic and pharmacological manipulations of dependence and withdrawal further support a role for calcium channels in these phenomena.