Neuropharmacology Poster Session
Martin-Iverson, M.T. (Depts. Psychology, Psychiatry & Pharmacology, University of Western Australia, Australia)
This study investigated the putative role of the steroid hormone, corticosterone, in the development of a circadian pattern of tolerance and sensitisation to the motor stimulant effects of the dopamine (DA) D2 agonist, (+)-4-propyl-9-hydroxynaphthoxazine (PHNO). Male Wistar rats were given continuous infusions of PHNO (5 mg/h) through subcutaneously implanted ALZETÒ osmotic minipumps. The animals showed a progressive decrease in motor response to PHNO (tolerance) over successive days and a progressive increase in motor response (sensitisation) over successive nights. Mild stress was found to increase motor activity in vehicle-infused controls and to reverse diurnal tolerance in PHNO-infused rats. Administration of a corticosterone synthesis inhibitor (metyrapone, 100 mg/kg) blocked stress-induced activity in controls, but did not block the stress-induced reversal of tolerance in the PHNO-treated group. Nocturnal metyrapone injections (100 mg/kg) did not reverse nocturnal sensitisation. A synthetic glucocorticoid (dexamethasone, 500 mg/kg) did not augment the effects of injection-stress. These results suggest that corticosterone release mediates the motor stimulant effects of stress in normal rats but does not mediate stress-induced sensitisation or circadian rhythms in the development of tolerance and sensitisation to the motor effects of PHNO.
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|Woodman, M.; Martin-Iverson, M.T.; (1998). Corticosterone Does Not Mediate the Development of Tolerance and Sensitisation to (+)-4-propyl-9-hydroxynaphthoxazine (PHNO). Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/neuropharm/woodman0565/index.html|
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