Modification of the effects of 7-OH-DPAT, a dopamine D3-receptor agonist, on morphine-induced hyperlocomotion by diabetes.
We examined the effect of 7-OH-DPAT on spontaneous locomotor activity that is enhanced in diabetic mice. 7-OH-DPAT (0.1-30 mg/kg, s.c.) dose-dependently decreased the enhanced spontaneous locomotor activity in diabetic mice, but not in nondiabetic mice. When mice were pretreated with of 7-OH-DPAT (0.1 mg/kg), morphine-induced enhanced locomotor activity in nondiabetic mice, but not in diabetic mice, was significantly reduced. Furthermore, 7-OH-DPAT (0.1 mg/kg) significantly attenuated the morphine-induced increase in DA turnover in both nondiabetic and diabetic mice. However, DA turnover was significantly greater in diabetic mice than in nondiabetic mice. Thus, it is likely that the enhanced spontaneous locomotor activity in diabetic mice may be partially related to the down-regulation of D3-receptor-mediated modulation of dopamine release in the limbic area.
Kamei
J
J
Department of Pathophysiology & Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Saitoh
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D009833:Olfactory Pathways / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D012016:Reference Values; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D015102:3,4-Dihydroxyphenylacetic Acid; D009020:Morphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine; D006719:Homovanillic Acid