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Calcium channel inhibitors suppress the morphine‐withdrawal syndrome in rats
Author(s) -
Bongianni F.,
Carla' V.,
Moroni F.,
PellegriniGiampietro D.E.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10236.x
Subject(s) - morphine , calcium channel , withdrawal syndrome , calcium , pharmacology , voltage dependent calcium channel , medicine , chemistry , neuroscience , anesthesia , psychology
1 The effects of the Ca 2+ ‐channel blockers verapamil and nimodipine, on the behavioural signs of naloxone (1 mg kg −1 )‐induced abstinence syndrome in morphine‐dependent rats, were evaluated. The content of noradrenaline (NA) and of its metabolite 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) was measured, using high performance liquid chromatography and electrochemical detection or gas chromatography‐mass spectrometry, in various brain regions of these animals. Possible interactions of nimodipine and verapamil with opioid receptors were evaluated by examining their ability to displace [ 3 H]‐naloxone binding to brain membranes. 2 Verapamil (5, 10 and 50 mg kg −1 ) and nimodipine (1,5 and 10 mg kg −1 ) dose‐dependently reduced most of the signs of morphine abstinence. 3 Naloxone‐precipitated abstinence decreased the NA content in the cortex, hippocampus, brainstem and cerebellum. In the same brain regions the content of MHPG increased, suggesting an increased release of the amine during morphine abstinence. 4 Nimodipine (10 mg kg −1 i.v.) did not change the content of NA or MHPG in the cortex, hippocampus and brainstem. However, nimodipine pre‐treatment markedly reduced the changes in NA and MHPG content induced by the abstinence syndrome. 5 Neither verapamil nor nimodipine displaced [ 3 H]‐naloxone from its binding sites. 6 These results suggest that Ca 2+ ‐channel blockers suppress the behavioural and neurochemical expressions of morphine abstinence by a mechanism that differs from those of opioids or α 2 ‐adrenoceptor agonists.