Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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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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Poster Number PAwoodman0565
Keywords: sensitization, dopamine, D2 receptor, steroids, stress