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Original Article

Neuronal calcium channels blocker, ziconotide (ɷ-conotoxin MVIIA), reverses morphine withdrawal-induced memory impairments via alteration in hippocampal NMDA receptor expression in rats

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Pages 323-332 | Received 24 Jan 2018, Accepted 14 Sep 2018, Published online: 26 Dec 2018
 

Abstract

ɷ-Conotoxin MVIIA (ziconotide or SNX-111) is an atypical analgesic drug with the water-soluble formulation and routinely is injected into the brain and spinal regions in human and animal model studies. The aim of the current study was to investigate the neurobehavioral protection of this agent as a selective N-type calcium channels antagonist following spontaneous morphine withdrawal in rats. Male rats were administered morphine (10–50 mg/kg) intraperitoneal (IP) twice daily for 7 days. Ziconotide was injected intrathecal (IT) either in chronic form (0.1, 0.3 and 1 µg/rat) concurrent with daily doses of morphine or it was injected as a single dose (1 µg/rat) on the last day. Novel object recognition task (NOR) and radial arm maze (RAM) were used in order to evaluation of the recognition and spatial working/reference memory performances, respectively. The amount of N-methyl-D-aspartate (NMDA) receptor subunits including NR2A and NR2B in the hippocampus and prefrontal cortex were determined by western blotting. We observed that abrupt cessation after chronic exposure to morphine led to decrease in both recognition and working/reference memory performances (p < .01). Spontaneous withdrawal also significantly suppressed the amount of NR2A and NR2B. This impairment was attenuated by single and chronic doses of ziconotide (p < .05). Also, expression of NR2A and NR2B were significantly increased during both drug delivery protocols. Our findings suggest that ziconotide prevents morphine withdrawal-induced memory deficits through alteration in glutamatergic transmission and regulation of NMDA receptors (NMDARs).

Acknowledgments

The authors are thankful to the School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Also, they are grateful to Dr. Mitra Emami for her cooperation and assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

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