Date of Award

1989

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Pharmaceutical Sciences

Specialization

Pharmacy and Toxicology

First Advisor

Al Swonger

Abstract

Male Sprague Dawley rats implanted with bipolar stainless steel electrodes aimed at the medial forebrain bundle at the level of the hypothalamus were trained to self administer a rewarding current on a 20:10 DRP operant schedule. A procedure based on the psychophysical method of limits was used to determine the threshold of self administration for this stimulus. The effects of the B2-agonist albuterol (salbutamol) on threshold, rearing, and motor activity were examined prior to and after a 19 day period of daily administration of either desipramine 10 mg/kg, fluoxetine 10 mg/kg, or saline.

Acute administration of albuterol 10 mg/kg caused a significant increase in thresholds and decrease in motor activity and rearing when compared to the three saline days prior to and post administration. Rats tested after 19 days of receiving desipramine daily or saline showed a similar increase in threshold when dosed with the albuterol 10 mg/kg while the group treated with fluoxetine 10 mg/kg daily did not. The albuterol caused a pronounced drop in motor activity and rearing regardless of prior chronic drug treatment. These results are consistent with a down regulation of B2-receptors by chronic administration of fluoxetine but not by desipramine or saline.

Acute administration of desipramine, fluoxetine, or saline did not cause any change in self stimulation threshold, though decreases in horizontal motor activity were seen with the antidepressants but not saline. Chronic daily administration of these antidepressants for 19 days resulted m a decrease m motor activity over time as compared to the saline treated animals. However, thresholds for rewarding stimulation were not affected by chronic treatment with antidepressant.

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