Potentiation of morphine-induced conditioned place preference with concurrent use of amantadine and fluvoxamine by the intraperitoneal and intracerebroventricular injection in rat.

Full Abstract

In this study, the effect of concurrent use of fluvoxamine and amantadine on morphine-induced conditioned place preference (CPP) was investigated by the intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection in rat. The CPP paradigms took place on 6 consecutive days by using an unbiased procedure. Our results showed that i.p. injection of morphine sulfate (2.5-10mg/kg) induced CPP in rat. On day 6, fluvoxamine (5 and 10mg/kg, i.p.), and amantadine (5 and 10mg/kg, i.p.) both increased morphine-induced conditioned place preference. Intracerebroventricular injection of fluvoxamine (10 microg/rat) and amantadine (10 microg/rat) were also increased morphine-induced conditioned preference significantly. Concurrent use of fluvoxamine (5mg/kg, i.p.; 10 microg/rat i.c.v.) and amantadine (10mg/kg, i.p.; 10 microg/rat, i.c.v.) potentiated morphine-induced conditioned preference significantly. Release of dopamine from neurons cause reinforcing behavior. Morphine produces reinforcement (reward) effect by activation of mu receptors which facilitated dopaminergic transmission through dopamine release. Fluvoxamine, a serotonin reuptake inhibitor, increase serotonin concentration in synaptic clefts, which is a potent stimulator of dopamine release. Amantadine also appears to work by increasing dopamine release from neuron. In conclusion, our results show that concurrent use of fluvoxamine and amantadine potentiate morphine-like effect on CPP through increasing dopaminergic transmission and this combination may simulate the rewarding effect of morphine and can be candidate for controlling the drug compulsive seeking in morphine dependent subjects.

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Author information

Author/s: Maleki, Saeid Abbasi (SA); Samini, Morteza (M); Babapour, Vahab (V); Mehr, Shahram Ejtemaei (SE); Cheraghiyan, Siyamak (S); Nouri, Mir H Khayat (MH);

Affiliation: Department of Pharmacology, School of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Journal and publication information

Publication Type: Comparative Study; Journal Article

Journal: Behavioural brain research (Behav Brain Res), published in Netherlands. (Language: eng)

Reference: 2008-Jul; vol 190 (issue 2) : pp 189-92

Dates: Created 2008/04/28; Completed 2008/07/30;

PMID: 18378011, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amantadine - administration & dosage
Animals
Association Learning - drug effects
Behavior, Animal - drug effects
Conditioning, Classical - drug effects
Dopamine Agents - administration & dosage
Drug Synergism
Fluvoxamine - administration & dosage
Injections, Intraperitoneal

Injections, Intraperitoneal
Injections, Intraventricular
Male
Morphine - administration & dosage; pharmacology
Narcotics - administration & dosage; pharmacology
Rats
Rats, Wistar
Reward
Serotonin Uptake Inhibitors - administration & dosage

Associated Chemicals: Dopamine Agents (0) ; Narcotics (0) ; Serotonin Uptake Inhibitors (0) ; Fluvoxamine (54739-18-3) ; Morphine (57-27-2) ; Amantadine (768-94-5)

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