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The effects of chronic administration of Buprenorphine on intake of heroin and cocaine in rats : behavioral and neurochemical interactions

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The effects of chronic administration of Buprenorphine on intake of heroin and cocaine in rats : behavioral and neurochemical interactions

Sorge, Robert E (2006) The effects of chronic administration of Buprenorphine on intake of heroin and cocaine in rats : behavioral and neurochemical interactions. PhD thesis, Concordia University.

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Abstract

Buprenorphine is a mu opioid receptor agonist used in the treatment of opioid abuse. Buprenorphine effectively reduces opioid intake in opioid abuse patients, but there is evidence that it is effective in reducing cocaine intake in a subset of individuals as well. Chronic administration of buprenorphine was achieved via the use of subcutaneously-implanted, buprenorphine-filled, osmotic minipumps in male rats. Chronic buprenorphine reduced heroin and cocaine seeking under extinction conditions and in tests of drug-induced reinstatement in rats trained to self-administer both drugs. The reduction in responding for drug in extinction and in tests for reinstatement was not due to locomotor sedation, as chronic buprenorphine slightly elevated locomotor activity. Furthermore, this common reduction cannot be explained via unique interactions with the abused drugs. Chronic buprenorphine had no effect on locomotor activity following acute injections of heroin, in spite of a blockade in the nucleus accumbens (NAc) dopamine (DA) response to this drug. On the other hand, chronic buprenorphine potentiated the locomotor and NAc DA responses to acute injections of cocaine. The interactions between buprenorphine and heroin and cocaine on NAc DA were further replicated during self-administration of heroin and cocaine. Buprenorphine had no effect on heroin self-administration at any dose or under any schedule of reinforcement although the NAc DA response to infusions was completely blocked. In contrast, cocaine self-administration was reduced under all schedules and doses in spite of a potentiated NAc DA response to infusions of cocaine. In all cases, buprenorphine levels in plasma and basal NAc DA levels were increased throughout chronic treatment, suggesting continuous receptor occupation. Although the mechanisms for the variable effects of buprenorphine on self-administration are unclear, a mechanism for the common reduction in responsiveness to drug-associated cues is proposed. The elevated basal levels of DA may have reduced the impact of the firing of DA neurons in response to cues; alternatively buprenorphine may have had its effect by reducing glutamatergic activity. There is reason to believe that buprenorphine could reduce glutamatergic activity and it is known that a reduction in glutamate transmission can disrupt responding for cues associated with drugs of abuse.

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Thesis (PhD)
Authors:Sorge, Robert E
Pagination:xii, 160 leaves : ill. ; 29 cm.
Institution:Concordia University
Degree Name:Ph. D.
Program:Psychology
Date:2006
Thesis Supervisor(s):Stewart, Jane
ID Code:9106
Deposited By:Concordia University Libraries
Deposited On:18 Aug 2011 14:44
Last Modified:18 Aug 2011 14:44
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