Selfadministration of methohexital midazolam and

Authors: Jillian H Broadbear Gail Winger James H Woods

Publish Date: 2004/08/21

Volume: 178, Issue: 1, Pages: 83-91

PDF Link

Abstract

There is disagreement in the literature with respect to how drugs of abuse affect the functioning of the hypothalamic–pituitary–adrenal HPA axis and whether these changes in endocrine function may be related to the rewarding effects of these drugsSeven monkeys 6 male were randomly assigned to selfadminister methohexital—a barbiturate n=4 midazolam—a benzodiazepine n=3 or ethanol n=5 Each monkey had a surgically implanted indwelling venous catheter and was trained to respond on a fixed ratio of 30 lever presses to receive an injection of drug or saline Blood samples were obtained before during and after the selfadministration sessions for the measurement of ACTH and cortisol by radioimmunoassayAlthough methohexital midazolam and ethanol all maintained selfadministration behavior across a range of doses they differed in their effects on ACTH and cortisol Ethanol inhibited ACTH and cortisol secretion Methohexital and midazolam both tended to decrease ACTH and cortisol at large doses and increase these hormones at small doses but the HPA effects of neither drug differed significantly from when saline was availableThe neutral overall effect of methohexital and midazolam on HPA activity is consistent with other monkey and human studies whereas the inhibitory effect of selfadministered ethanol in the monkey contrasts with both the rat and human literature The data in this study suggest that a change in HPA axis activity is not a requirement for drugreinforced behavior in monkeysThe authors wish to thank Nicholas Jones Deborah Huntzinger Sarah Pilkington and Laurie McDowell for their expert technical assistance Animals used in these studies were maintained in accordance with the “Principles of laboratory animal care” http//wwwnapedu/readingroom/books/labrats/ and all studies reported here were carried out in consultation with the University of Michigan Committee on Animal Care and Guidelines of the Committee on the Care and Use of Laboratory Animal Resources National Health Council Department of Health Education and Welfare ISBN 0309053773 revised 1996 This work was supported by the United States Public Health Service Grants DA 0916 DA 00254 and AA13783

Keywords: