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Dissertation
Identification of central nervous system structures involved in mediating conditioned hyperactivity responses to a cocaine-paired environment
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania and Hahnemann University
Oct 1999
DOI:
https://doi.org/10.17918/00008898
Abstract
Conditioned hyperactivity in rats may be related to the excited state that human cocaine abusers report following exposure to drug-related stimuli and may contribute to craving. Therefore, this model can be used to investigate the neurobiological processes underlying the associations made between the effects of cocaine and environmental stimuli in humans. A better understanding of the neurobiology underlying this Pavlovian conditioned response will aid in the development of pharmacotherapies that can prevent cravings in abstinent individuals wishing to remain drug-free. This thesis used two different methodologies and the conditioned hyperactivity model to examine the participation of forebrain regions in rats exposed to an environment previously paired with cocaine. Method 1 involved quantifying the expression of fos-related antigens (FRAs) in forebrain regions following a test for conditioned hyperactivity. Method 2 consisted of functionally inhibiting select CNS regions implicated in mediating the Pavlovian conditioned response prior to a test for conditioning. For each experiment, rats were conditioned by repeatedly exposing them to an environment either paired (Paired group) or explicitly unpaired (Unpaired group) with systemic cocaine injections. The preliminary and FRA experiments included a Control group that never received cocaine. In all experiments, a subsequent cocaine-free test for conditioning revealed that the Paired group was hyperactive relative to Unpaired and Control groups. FRA expression measured following the conditioning test revealed a significant and selective context-dependent enhancement of FRA-positive nuclei in the caudal nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC) of the Paired group relative to the Unpaired and Control groups. Subsequent experiments used the second method, functional inhibition of select CNS regions, to further examine the participation of the basolateral amygdala, ventral subiculum, mPFC, secondary motor cortex, NAc and the caudate nucleus in mediating conditioned hyperactivity. Conditioned hyperactivity responses were prevented by GABA agonist infusions into the mPFC and the NAc prior to the conditioning test, but not in other regions tested. Both techniques led to the conclusion that the mPFC and the NAc are crucial elements of the neural circuitry underlying the expression of conditioned hyperactivity responses to cocaine-related stimuli.
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Details
- Title
- Identification of central nervous system structures involved in mediating conditioned hyperactivity responses to a cocaine-paired environment
- Creators
- Teresa R. Franklin
- Awarding Institution
- Medical College of Pennsylvania and Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania and Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- x, 141 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Other Identifier
- 991021888866704721