Pinealectomy blocks stress-induced motor stimulation but not sensitization and tolerance to a dopamine D2 receptor agonist.
BACKGROUND
The motor stimulant effects of the selective dopamine D2 receptor agonist, (+)-4-propyl-9-hydroxynaphthoxazine (PHNO), develop both tolerance and sensitization depending on circadian rhythms and time of day. Daytime tolerance can be transiently reversed by stress. Given that only tolerance develops when rats are kept under constant light conditions, it seems plausible that the pineal hormone melatonin may determine the circadian rhythm in tolerance and sensitization.


OBJECTIVE
The effects of pinealectomy on the development of sensitization and stress-induced reversal of tolerance to sensitization to the motor stimulant effects of PHNO were determined.


METHODS
Sprague-Dawley rats were pinealectomized or given sham operations and administered continuously with PHNO (5 microg/h) via subcutaneously implanted mini-pumps. Injections of 2-iodo-melatonin were subsequently administered to determine if sensitization to PHNO could be reinstated in the pinealectomized animals, assuming that sensitization would be reduced.


RESULTS
Pinealectomy did not influence circadian rhythms in the development of sensitization and tolerance to PHNO. Pinealectomy blocked the motor activation effects of "injection-stress", and this effect was reinstated by treatment with 2-iodo-melatonin.


CONCLUSIONS
Melatonin is not involved in the development of sensitization or tolerance to the behavioral effects of PHNO. However, melatonin modulates the stress-induced motor activity responses.
Ruzich
M
M
Department of Psychology, University of Western Australia, Perth, Nedlands, Australia.
Martin-Iverson
M T
MT
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D004361:Drug Tolerance; D008550:Melatonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects*; D010078:Oxazines / Q000494:pharmacology*; D010870:Pineal Gland / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013312:Stress, Physiological / Q000523:psychology*
D018491:Dopamine Agonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; C042631:naxagolide; C044556:2-iodomelatonin; D008550:Melatonin