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https://hdl.handle.net/2142/71348
Description
Title
Benzodiazepines and Dopamine Mediated Behavior
Author(s)
O'Brien, Dennis Paul
Issue Date
1987
Doctoral Committee Chair(s)
White, Francis
Department of Study
Veterinary Medical Science
Discipline
Veterinary Medical Science
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Neuroscience
Abstract
These studies assess the effects of dopamine depleting lesions on behavior and the effects of benzodiazepines on catalepsy and the ventral tegmental area.
The first experiment demonstrated that specific physical stimuli (tail-pinch and vestibular) activated specific components of behavior (feeding and locomotion, respectively) in cats made cataleptic and aphagic by lateral hypothalmic lesions. In preliminary trials in such cats, as well as rats with more specific 6-hydroxydopamine lesions of dopaminergic neurons, diazepam failed to produce a similar activation. Rather it appeared to diminish the catalepsy.
The second experiment demonstrated that diazepam did indeed diminish the enhanced postural support seen in cataleptic, haloperidol-treated rats. These results were contrary to the theory that diazepam enhanced catalepsy.
The final experiment used extracellular single unit recordings to directly study the effects of benzodiazepines in the ventral tegmental area. Intravenous diazepam produced a significant excitation of dopaminergic cells. When haloperidol-treated rats were given diazepam, the dopamine cells showed no significant change in firing. Only one dopamine cell showed a decrease in firing rate and this was accompanied by changes in waveform suggesting a depolarization block. Iontophoresis of benzodiazepines onto dopamine cells had no effect. Both intravenous and iontophoretic benzodiazepines produced a profound inhibition of firing of non-dopamine cells in the ventral tegmental area.
From these studies, I conclude that physical stimuli can activate specific components of behavior in otherwise cataleptic, akinetic animals. Benzodiazepines do not reinstate behavior as the physical stimuli would. They also do not enhance catalepsy but rather deactivate the exaggerated postural support characteristic of catalepsy. Thus, the behavioral data does not support the theory that benzodiazepines enhance feedback inhibition of dopamine cells. Indeed, based on single unit recordings in the ventral tegmental area, benzodiazepines produces an indirect excitation of dopaminergic neurons, probably via disinhibition. Non-dopamine cells were directly inhibited by benzodiazepines. Thus, if these non-dopamine cells were interneurons which tonically inhibited the dopamine cells, then the inhibition of these non-dopaminergic cells could produce the excitation seen in the dopaminergic cells.
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