The goal of this dissertation was to investigate the role of μ-opioid receptors in
the mechanism of ethanol-stimulated dopamine release in the nucleus
accumbens shell (NAcS) of rats. The underlying hypothesis is that blockade of
the μ-opioid receptors leads to an attenuation of ethanol-stimulated mesolimbic
dopamine release. We prepared ethanol-naïve male Long Evans rats (n = 95) for
intravenous (i.v.) drug administration and in vivo microdialysis (in awake, freely
moving animals), and analyzed our samples using HPLC and GC for dopamine
and ethanol detection, respectively. In one set of experiments, we looked at the
effects of naltrexone, a non-selective opioid antagonist, on ethanol-stimulated
mesolimbic dopamine release. First of all, we checked to see if naltrexone
affected basal dopamine levels in the NAcS. Thereafter, we looked for a dose of
naltrexone (i.v.) that was effective in suppressing the release of dopamine in the
NAcS evoked by morphine (1 mg/kg, i.v.). Subsequently, we checked to see if
doses of naltrexone that inhibited morphine-evoked dopamine were also effective in attenuating dopamine release due to ethanol (1g/kg, 10% w/v, i.v.). To do this,
we pretreated rats with naltrexone doses, followed 20 min later by morphine,
ethanol or saline (all drugs were administered i.v.). In another set of experiments,
we looked at the effect of β-funaltrexamine, a selective μ-opioid antagonist, on
ethanol-stimulated dopamine release in the NAcS. Similarly to the previous set of
experiments, we looked for a dose of β-funaltrexamine (s.c.) that was effective in
suppressing the release of dopamine the NAcS evoked by morphine (1 mg/kg,
i.v.), and checked to see if this dose of β-funaltrexamine was also effective in
attenuating ethanol-stimulated dopamine release in the NAcS. For the β-
funaltrexamine experiments, rats were pretreated with β-funaltrexamine (s.c.) 20-
25 h before i.v. infusions of saline, morphine and ethanol.
Morphine increased dopamine release in the NAcS. Naltrexone and β-
funaltrexamine significantly attenuated morphine-evoked dopamine release.
Also, ethanol increased dopamine release in the NAcS. Naltrexone and β-
funaltrexamine, at doses effective in attenuating morphine-evoked dopamine
release, suppressed the prolongation, but not the initiation of dopamine release
in the NAcS due to ethanol. Naltrexone and β-funaltrexamine did not affect the
peak concentration and clearance of ethanol in the brain. The conclusion of this
study is that the μ-opioid receptors are involved in a delayed component of
ethanol-stimulated dopamine release in the NAcS in ethanol-naïve rats. This is
the first study to show that the ethanol-stimulated dopamine response consists of
a delayed μ-opioid mechanism. / text
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/6901 |
| Date | 05 February 2010 |
| Creators | Job, Martin Olufemi |
| Source Sets | University of Texas |
| Language | English |
| Detected Language | English |
| Format | electronic |
| Rights | Copyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works. |
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