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Dissertation
Anatomical characterization of inhibitory local circuit neurons in the anterior cingulate cortex of rats following repeated exposure to amphetamine or nicotine
Doctor of Philosophy (Ph.D.), Drexel University
Jul 2003
DOI:
https://doi.org/10.17918/00009032
Abstract
Repeated administration of drugs of abuse, including psychostimulants, leads to progressive increases in the psychomotor stimulatory effects of these drugs. This increase in drug effect is known as psychomotor sensitization and is believed to model drug addiction, as the neural systems that mediate psychomotor sensitization are also believed to mediate the rewarding aspects of drugs of abuse. Anatomical and electrophysiological studies have revealed that repeated administration of amphetamine (AMPH) results in changes in the prefrontal cortex (PFC) consistent with modified synaptic organization and enhanced cortical connectivity with subcortical structures. Using anatomical techniques, the present study examines changes in classes of local circuit interneurons in the anterior cingulated cortex (ACC) of rats following exposure to drugs of abuse, in particular, the psychostimulant AMPH, which may contribute to the cortical pathophysiology observed in drug addiction. We observed selective increases in the density of parvalbumin (PV), but not calbindin (CB) or calretinin (CR), immunoreactive (ir) interneurons in the ACC of AMPH-treated rats at 1-day and 7-day withdrawal. Consistent with the idea that mesocortical DA is critically involved in neural changes following exposure to drugs of abuse, we observed a selective increase in PV-ir interneurons in the ACC following repeated treatment with apomorphine (D1/D2 agonist) and SKF-38393 (D1 agonist) at 1-day, but not at 7-day, withdrawal from drug treatment. Additionally, we observed an increase in CRF-ir puncta in the ACC of AMPH-treated rats at 7-day, but not at 1-day, withdrawal that were found to surround PV-ir cells, but not CB-, CR-, or glutamate-containing cell bodies. To further examine alterations in GABA interneurons following exposure to drugs of abuse, we performed similar studies in rats exposed to the psychostimulant drug of abuse nicotine (NIC). We observed selective increases in the density of both PV- and CR- (but not CB-) it interneurons in the ACC of rats receiving chronic oral administration of nicotine at Q-day withdrawal, with no changes in the densities following 7-day withdrawal. In summary, we revealed the PV-ir class of interneurons is selectively altered in the ACC following AMPH treatment; these alterations are mediated, at least in part, by dopamine-receptor stimulation. Furthermore, CRF-mediated pathways may mediate changes in PV-ir interneurons that persist into AMPH withdrawal. Moreover, chronic nicotine treatment appears to selectively alter PV- and CR-ir only during the treatment period. Together these studies indicate that changes in PV-ir interneurons may be a common link in cortical deficits observed following exposure to drugs of abuse.
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Details
- Title
- Anatomical characterization of inhibitory local circuit neurons in the anterior cingulate cortex of rats following repeated exposure to amphetamine or nicotine
- Creators
- Carrie Ann Mohila
- Contributors
- Shao-Pii Onn (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xv, 218 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 991021889091804721