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Neural Activity Associated with Tolerance to Amphetamine Hypophagia

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Date Issued:
2006
Summary:
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.
Title: Neural Activity Associated with Tolerance to Amphetamine Hypophagia.
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Name(s): Bachand, Kimberlee D., author
Wolgin, David L., Thesis advisor
Florida Atlantic University, Degree grantor
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2006
Date Issued: 2006
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 299 p.
Language(s): English
Summary: 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.
Identifier: FA00000847 (IID)
Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2006.
Subject(s): Amphetamines--Physiological effect
Drug tolerance
Drugs--Physiological effect
Rats as laboratory animals
Held by: Florida Atlantic University Libraries
Sublocation: Digital Library
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00000847
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Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.