The involvement of dopamine (DA) in the emotional and psychiatric disturbances associated with schizophrenia and psychomotor stimulant abuse is well known; however, the mechanism by which DA mediates fear expression and anxiety is not well defined. Accordingly, the objective of the present thesis was to determine the fear-motivational functions of DA neurons in the ventral tegmental area (VTA) and to examine the role of DA in fear extinction using the potentiated startle paradigm. In Experiment 1, it was observed that electrical stimulation of the VTA produced a pronounced increase in the amplitude of the acoustic startle reflex. In subsequent experiments fear-potentiated startle was assessed following axon-sparing N-methyl-D-aspartic acid (NMDA) lesions of the VTA and after bilateral intra-VTA infusion of the DA D<sub>2/3</sub> receptor agonist quinpirole (Experiments 2-4). The NMDA lesions resulted in substantial cell loss in the medial ventral tegmentum and blocked fear-potentiated startle. Similarly, inhibition of DA neuronal activity associated with locally-administered quinpirole suppressed the expression of the conditioned fear-induced increase in startle amplitudes. The quinpirole results implicate DA neuronal functioning in fear motivation. To explore further the involvement of DA in aversive emotional behavior, pharmacological experiments were conducted in which the effects of peripherally-administered DA agonist drugs on fear extinction were assessed. Subjects in Experiment 5 received an acute injection of either cocaine hydrochloride (40.0 mg/kg), d-amphetamine sulphate (5.0 mg/kg), the D<sub>2/3</sub> agonist quinpirole hydrochloride (5.0 mg/kg), or the D<sub>1</sub>-type agonist SKF 38393 (5.0 mg/kg) during a single extinction session following fear acquisition. Animals treated with cocaine, d-amphetamine, and SKF 38393 exhibited fear-potentiated startle, whereas quinpirole treatment failed to alter fear extinction to the nonreinforced conditioned stimulus (CS). Also, it was revealed using a within-subjects design in Experiment 6 that cocaine administration reinstated fear-potentiated startle following extinction. Taken together, the results of the present experiments suggests fundamental role for DA and DA D<sub>1</sub> receptors in fear expression. It was proposed that VTA DA neurons gate levels of aversive emotional arousal within the amygdala-based fear system.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-10212004-000803 |
| Date | 01 January 1997 |
| Creators | Borowski, Thomas Brian |
| Contributors | Cheesman, James E. (Jim) |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-10212004-000803 |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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