Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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Continuous treatment of rats with the selective dopamine D2 agonist, (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) results in the development of sensitisation at night and tolerance during the day to PHNO's (0.005 mg/hour) motor stimulant effects. Mild stress can reverse daytime tolerance to sensitisation and augment nocturnal effects of PHNO. The possibility that the development of sensitisation and tolerance depends on circadian or stress-induced release of melatonin was assessed by investigating PHNO's effects in pinealectomised rats maintained on a 12:12 LD cycle. Daytime tolerance and nocturnal sensitisation occurred to PHNO in rats regardless of whether they had pinealectomies or sham-operations (n = 12 for both groups). Stress increased nocturnal motor activity in both PHNO and vehicle treated sham-operated groups. Pinealectomy prevented this stress-induced increase in activity, and stress effects on motor activity were restored in pinealectomised rats by administration of the melatonin agonist, 2-iodomelatonin (0.5 mg/kg, IP). It can be concluded that melatonin does not contribute to the nocturnal sensitisation to PHNO, and that the daytime tolerance to PHNO is not likely due to light-induced suppression of melatonin release. On the other hand, melatonin appears to contribute to stress-induced increases in motor activity in both vehicle and PHNO treated rats.

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Poster Number PAruzich0646
Keywords: melatonin, chronic treatment, rat, osmotic pumps, sensitization