Synergistic behavioural effects of dopamine D1 and D2 receptor agonists are determined by circadian rhythms. 1992

M T Martin-Iverson, and N Yamada
Department of Psychiatry, University of Alberta, Edmonton, Canada.

The effects of continuous subcutaneous infusions of rats for 336 h with vehicle, SKF 38393 (a dopamine D1 receptor agonist), (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, a dopamine D2 receptor agonist) or both D1 and D2 receptor agonists, on locomotor activity were investigated. Rats were maintained under constant lighting conditions, either continuous dark (dark:dark) or continuous light (light:light), before and during drug treatments in order to determine the influence of free-running circadian rhythms on drug responses. The D2 receptor agonist initially increased locomotion in rats kept under dark:dark during both subjective night (period of maximum locomotion) and day (period of minimum locomotion), but had no effect in rats maintained in light:light throughout the 336 h of treatment. The motor stimulant effects of the D2 receptor agonist on rats kept in dark:dark increase during the course of treatment during subjective night (sensitization), but decreased during the rats' subjective day (tolerance). The D1 receptor agonist, SKF 38393, had no effect on its own regardless of the lighting conditions and the duration of treatment. However, the D1 receptor agonist interacted synergistically with the D2 receptor agonist in rats maintained under light:light, depending on the duration of treatment. Synergistic effects were also observed on initiation of treatment in rats under dark:dark but only during subjective day. Tolerance to the synergistic effects of the receptor agonists occurred as a function of treatment duration, but only during subjective day. The D1 receptor agonist blocked the effects of the D2 receptor agonist during the rats' subjective night after 100 h of treatment, but not after 25 or 325 h.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008027 Light That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range. Light, Visible,Photoradiation,Radiation, Visible,Visible Radiation,Photoradiations,Radiations, Visible,Visible Light,Visible Radiations
D008124 Locomotion Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. Locomotor Activity,Activities, Locomotor,Activity, Locomotor,Locomotor Activities
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D010078 Oxazines Six-membered heterocycles containing an oxygen and a nitrogen.
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D003624 Darkness The absence of light. Darknesses
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug

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