NEUROCHEMICAL PROFILE IN THE NUCLEUS ACCUMBENS DURING DEVALUATION OF NATURAL REWARDS IN DRUG ADDICTION

Open Access
Author:
Douton, Joaquin E
Graduate Program:
Neuroscience
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
August 15, 2016
Committee Members:
  • Dr. Patricia Sue Grigson, Thesis Advisor
  • Dr. Robert Levenson, Committee Member
  • Dr. Andras Hajnal, Committee Member
  • Dr. Scott Bunce, Committee Member
Keywords:
  • Reward devaluation
  • Cocaine
  • Heroin
  • Taste Reactivity Test
  • Microdialysis
Abstract:
Devaluation of natural rewards is a devastating consequence of drug addiction. Drugs of abuse hijack the innate reward system and reorient it towards drug-seeking and drug-taking to the detriment of behaviors involving the seeking of standard natural rewards. In the animal model of reward devaluation, rats avoid intake of an otherwise palatable saccharin solution when it predicts the availability of a drug of abuse (e.g., morphine, cocaine or heroin). Greater avoidance predicts greater drug-seeking and taking. That being said, it is not immediately clear why rats avoid the saccharin cue. One hypothesis is that the taste cue simply become aversive as a result of its association with drug. If so, the neurochemical response elicited in the nucleus accumbens by the drug-paired cue should parallel that obtained following intraoral delivery of a known aversive stimulus such as quinine (QHCl). Therefore, the goal of this thesis is to determine the neurochemical profile for rewarding (i.e., sucrose and saccharin) and aversive (i.e., quinine) stimuli and to compare those profiles with those obtained for a saccharin cue that was paired with the opportunity to self-administer heroin or cocaine. To this end, Chapter 2 collected samples from the nucleus accumbens (NAc) using microdialysis and analyzed those samples with a new method of ultra performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) that allows for the measurement of several neurochemicals from a single sample. The collection will occur while the animals consume, or are intraorally infused with, a sucrose or a quinine solution. The results of this experiment revealed different profiles for a rewarding and an aversive taste stimulus. Chapter 3 studied the neurochemical response in the NAc to a saccharin cue that was paired with the opportunity to self-administer a drug of abuse (i.e., heroin, cocaine). Following a series of such taste-drug pairings, microdialysis samples were collected while the animals received intraoral infusions of the drug-paired cue. Samples were analyzed using the same method as described in Chapter 2. The results showed changes in dopamine and other neurochemicals such as histamine, serine, glutamate, GABA and serotonin when rats were exposed to a drug-associated taste cue, particularly following an extended abstinence period. These patterns were similar to those found in response to quinine. Taken together, these data suggest the existence of a different neurochemical profile for a putatively rewarding and a putatively aversive taste stimulus and that a drug-paired cue shows changes similar to those observed in an aversive-like profile, particularly when tested following an extended period of abstinence. The drug-paired taste cue, then, may become aversive following abstinence and/or the cue may elicit the onset of an aversive withdrawal state.