Effect Of Rolipram, A Type 4-Specific Phosphodiesterase Inhibitor, On Unit Activity Of Paragigantocellularis Neurons And Withdrawal Signs In Morphine Dependent Rats

Document Type : Original Article

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PHYSIOLOGY DEPARTMENT, SCHOOL OF MEDICAL SCIENCES,TARBIAT MODARRES UNIVERSITY, TEHRAN, IRAN

Abstract

introduction: Effect of rolipram, as a type 4-specific phosphodiesterase inhibitor on spontaneous activity of paragigantocellularis nucleus (PGi) and precipitation of withdrawal signs in morphine dependent rats was studied.
Material and Methods: Extracellular single unit recording was used to record the spontaneous activity of PGi neurons in urethane-anesthetized NMRI male rats (250-350g). Rolipram (0.1, 1 and 10 micro mol) was microinjected into PGi. To assess the behavioral signs, frequency analysis was used.
Results: The results showed that rolipram microinjection (0.1 and 1micro mol) in control rats had no significant effect on the spontaneous activity of the PGi neurons. Rolipram microinjection (10 ?M) in control rats increased and in morphine dependent ones decreased neuronal activity significantly. Intranuclear microinjection of rolipram (10 micro mol) produced chewing and teeth chattering in control rats while induced ejaculation and writhing in dependent ones. Restlessness, forepaw tremor, jumping and ptosis as withdrawal signs didn"t appear and signs such as teeth chattering and writhing decreased by applying 10 micro mol of rolipram into the PGi nucleus before subcutaneous injection of naloxone.
Conclusion: It is concluded that adaptive changes in activity of cAMP pathway in PGi neurons following chronic morphine exposure may play an important role in the development of dependence on morphine.

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Cell Journal (Yakhteh)
Volume 7, Issue 1
April 2005
Pages 35-42

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