The effect of intrathecal administration of the neuronal N-type calcium channels antagonist, omega-conotoxin MVIIA, on attenuating the spontaneous and naloxone-precipitated morphine withdrawal in rats

Abstract

The effect of -conotoxin MVIIA (Ziconotide or SNX-111) as an inhibitor of the neuronal N-type calcium channels on the signs of morphine withdrawal was investigated. The animals were rendered to physical dependence by the continuous intraperitoneal (IP) injections of gradually enhancing the doses of morphine (10-50mg/kg) during 7 days. The withdrawal was induced in animals through the IP administration of naloxone with the dose of 2mg/kg or it was elicited spontaneously. The single and chronic intrathecal injections of -conotoxin following the naloxone-precipitated withdrawal diminished the number of jumpings (p<0.05). Moreover, both acute and chronic administrations of the drug alleviated the intensity of ptosis, piloerection, teeth chattering, diarrhea, irritability and genital grooming (p<0.01) during the two models of the experiment. It can be concluded that the class of N-type calcium channel blockers ameliorate the severity of morphine withdrawal syndrome.