Prazosin inhibits spontaneous locomotor activity in diabetic mice.
We examined the effect of prazosin, a selective alpha1-adrenergic receptor antagonist, on the enhanced spontaneous locomotor activity in streptozotocin-induced diabetic mice. Spontaneous locomotor activity in diabetic mice was significantly greater than that in nondiabetic mice. Pretreatment with either intracerebroventricular (5, 10 nmol) or intraperitoneal (0.5, 1.0 mg/kg) injection of prazosin dose-dependently reduced the spontaneous locomotor activity in diabetic mice, but not in nondiabetic mice. Furthermore, the enhanced dopamine turnover ratio in the limbic forebrain in diabetic mice was reduced to the same level as that in nondiabetic mice after the administration of prazosin. Thus, these results suggest that alpha1-adrenergic receptors might play an important role in the enhanced spontaneous locomotor activity in diabetic mice. Furthermore, alpha1-adrenoceptor antagonism might have an inhibitory effect on presynaptic dopaminergic neurotransmission in the limbic forebrain in diabetic mice.
Saitoh
Akiyoshi
A
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan.
Onodera
Kenji
K
Morita
Kayo
K
Sodeyama
Midori
M
Kamei
Junzo
J
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D011224:Prazosin / Q000008:administration & dosage*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin