Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine

• Published in: Psychopharmacologia Vol. 111; no. 4; pp. 457 - 464
• Main Authors: ANTKIEWICZ-MICHALUK, L, MICHALUK, J, ROMANSKA, I, VETULANI, J
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-07-1993
• Subjects: Analgesics - pharmacology; Animals; Biological and medical sciences; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Drug Interactions; Drug Tolerance; Drug toxicity and drugs side effects treatment; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Morphine - pharmacology; Morphine Dependence - psychology; Nifedipine - pharmacology; Pain Measurement - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1 - drug effects; Receptors, Opioid - drug effects; Receptors, Opioid, mu - drug effects; Substance Withdrawal Syndrome - psychology; Weight Gain - drug effects; Drug combination; Intraperitoneal administration; Rat; Toxicity; Rodentia; Calcium antagonist; Tolerance; Morphine; Opiates; Narcotic analgesic; Dihydropyridine derivative; Prevention; Analgesia; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Dependence; Drug of abuse; Withdrawal syndrome
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/bf02253536

Nifedipine, 5 mg/kg IP, potentiated the morphine-induced analgesia measured in the hot-plate, but not in the tail-flick test. Further experiments were carried out using the hot-plate test only. Pretreatment with nifedipine partially restores the analgesic action of morphine in morphine-tolerant rats. Co-administration of nifedipine with morphine in a chronic experiment did not prevent the loss of morphine efficiency (an increase in latency of 44% was not significant) and did not prevent the debilitating effect of chronic morphine administration reflected by an inhibition of the body weight gain, but prevented naloxone-induced withdrawal syndrome (quantified by counting head shakes) in the test carried out 24 h after the injection of nifedipine, when the drug did not affect morphine analgesia. Chronic treatment with either morphine or nifedipine did not produce a significant increase in the density of [3H] naloxone or [3H]prazosin binding sites in the cortex and in the rest of the brain (measured 24 h after the last dose), but the combined treatment resulted in a significant increase in the cortical [3H]prazosin binding site density. The present results suggest that opiate tolerance and physical dependence may be separated by co-administration of nifedipine and suggest that the combined chronic treatment with morphine and nifedipine may increase the efficacy of morphine during chronic treatment and prevent development of abstinence.