THE INFLUENCE OF SOME CALCIUM CHANNEL BLOCKERS ON SOME ASPECTS OF LORAZEPAM ADDICTION

Abstract

Lorazepam is a drug of dependence; its abrupt withdrawal after prolonged treatment can I' lead to an bstinence syndrome. It was aimed to investigate experimentally the potential I usefulness of!; certain calcium channel blockers in protecting against lorazepam dependence in !' " mice. Dependence was induced by twice daily administration of LZ (1 mg kg•') for 10 days;

doubling the dose during the next 10 days. Withdrawal symptoms consisting of hypermotility, I

rigidity and/o(convulsions, were observed after 24h. withdrawal or tlumazenil administration.

•I At the same ti!Tie, norepinephrine (NE), dopamine (D) and serotonin (5-HT) contents were

determined in different brain regions. The effects of acute and chronic treatments of isradipine " (0.6 and 1.2 mg kg.1), diltiazem (10 and 20 mgkg.1) and tlunarizine (I and 2 mg kg.1 , were •' determined in control mice and in lorazepam dependent mice either after 24h. withdrawal or

flumazenil treatment. The following results were obtained. "

1- Lorazepain withdrawal symptoms in mice and changes in neurotransmitters in different brain regions. Flumazenilproduced more intense withdrawal symptoms than the 24h. withdrawal group in lorazepam depe dent mice. In both groups there was a significant increase in cerebral cortex NE contents! with rpuch higher percentage in the tlumazenil treated group. In addition, the later :• ,, group showed significant increase if NE in the thalamus hypothalamus region. No significant

change in D or 5-HT contents in different brain regions was recorded. .