Fluvoxamine on rat ethanol self-administration

  • Lamb, Richard J (PI)

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): There appears to be an inverse relationship between synaptic serotonergic throughput and alcohol consumption. A key piece of evidence for this is the effects of specific serotonin reuptake inhibitors (SSRIs) on ethanol consumption. However, because the mechanism(s) of these effects of SSRIs on ethanol consumption remains unknown, interpretation of these data remains ambiguous. Recently, we observed that the SSRI fluvoxamine reduces responding for ethanol at lower doses than those required to reduce responding for either food or sucrose solutions in rats. In this application, we propose to study the mechanism of these selective effects of fluvoxamine through three specific aims: I) extending our findings on fluvoxamine's selective effects; II) investigating the neurobiologic mechanisms of these selective effects; and III) investigating the behavioral mechanisms of the selective effects. We extend our findings by A) using a within-subject experimental design; B) showing clinically relevant ethanol consumption and C) determining if fluvoxamine and ethanol interact pharmacokinetically. Aim I systematically replicates our earlier findings and extends these findings by examining three explanations of our results: i) that the potency of fluvoxamine increases with chronic exposure to ethanol; ii) self-administered ethanol has direct pharmacological effects that act synergistically with fluvoxamine to decrease response-rates; and iii) fluvoxamine and ethanol interact pharmacokinetically. We examine the neurobiologic mechanisms of fluvoxamine's selective effects by A) examining if other antidepressants have selective effects; B) examining whether these selective effects, previously observed in Lewis rats, are also observed in Fischer and Sprague Dawley rats; and C) examining if repeated fluvoxamine has selective effects. These experiments narrow the field of potential neurobiologic mechanisms. We investigate possible behavioral mechanisms of fluvoxamine's selective effects by examining A) whether fluvoxamine has effects consistent with the hypothesis that fluvoxamine produces its selective effects by attenuating ethanol reinforcement, and B) whether fluvoxamine has effects consistent with other alternative hypotheses for these selective effects. Only by conducting experiments such as these can we delineate what the behavioral actions of fluvoxamine are that result in selective decreases in ethanol-seeking behavior and thus, what these selective decreases mean with regards to 1) the role of serotonin in the control of alcohol consumption and alcoholism, and 2) the treatment of alcoholism with SSRIs.
StatusFinished
Effective start/end date9/24/017/31/17

Funding

  • National Institutes of Health: $262,800.00
  • National Institutes of Health: $250,078.00
  • National Institutes of Health: $37,241.00
  • National Institutes of Health: $262,800.00
  • National Institutes of Health: $202,510.00
  • National Institutes of Health: $216,750.00
  • National Institutes of Health: $260,172.00
  • National Institutes of Health: $326,283.00
  • National Institutes of Health: $262,800.00
  • National Institutes of Health: $336,375.00
  • National Institutes of Health: $216,750.00
  • National Institutes of Health: $216,750.00
  • National Institutes of Health: $254,097.00

ASJC

  • Medicine(all)

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