Author Type

Graduate Student

Date of Award

2006

Document Type

Dissertation

Publication Status

Version of Record

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Wolgin, David L.

Abstract

There is a growing body of literature indicating that drug effects are influenced by the context in which they are taken, and that neuroadaptations resulting from chronic drug use are similarly context dependent. Contingent tolerance to amphetamine-induced hypophagia is mediated by the learned suppression of stereotyped behaviors, and is an example of a drug-environment interaction. This form of behavioral tolerance depends upon instrumental learning, by which rats learn a strategy to suppress drug-induced stereotypies that interfere with feeding. Considerable progress has been made in understanding contingent tolerance at the behavioral level; little is known about the neural mechanisms underlying contingent tolerance. Therefore, the purpose of this study was to delineate neural circuitry involved in contingent tolerance. The differential activation of neurons expressing the immediate early gene c-fos was analyzed throughout the brains of amphetamine-tolerant and non-tolerant rats, using the Before-After paradigm; the amphetamine tolerant group received injections of amphetamine (2.0 mg/kg) before access to milk, after-amphetamine and after-saline groups (i.e., nontolerant) received injections of amphetamine after access to milk, and the saline group received saline at both time points. The experimental design permitted us to identify structures uniquely involved in tolerance from those associated with drinking milk, having a history of amphetamine, or receiving an injection of amphetamine on the final test. The unique finding reported here is that when amphetamine is given in an environment containing food, patterns of c-fos are very different than when the drug is given in an environment without food. Results showed that amphetamine-tolerant animals had significant increases in c-fos in a set of interconnected structures throughout the brain, as compared with non-tolerant and saline rats. These data supported the hypothesis that structures associated with the dorsal striatum mediate the response selection of feeding and the inhibition of stereotypies, while the ventral striatum, via instrumental learning, reinforces the selection and inhibition of competing motor behaviors. Results also support the idea that the mechanisms of tolerance involve several neural subsystems that function to modulate motor, motivational, and reward-based learning. Specifically, the learned suppression of stereotypies involves the tolerance "Response Selection," "Reinforcement," and "Instrumental Learning" subsystems.

Extent

299 p.

Comments

Dissertation (Ph.D.)--Florida Atlantic University, 2006.|Dissertation (Ph.D.)--Florida Atlantic University, 2006.

Identifier

FA00000847

Format

pdf

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