title: Effects of sulpiride and nemonapride, benzamide derivatives having distinct potencies of antagonistic action on dopamine D2 receptors, on sensitization to methamphetamine in mice.
abstract: The acute ambulatory stimulation by methamphetamine (2 mg kg-1 S.C.) was dose-dependently reduced by 3-h pretreatment or combined treatment with sulpiride (1-100 mg kg-1 S.C.), and combined treatment with nemonapride (0.003-0.03 mg kg-1 S.C.), benzamide derivatives having selective antagonistic action on dopamine D2 receptors. The repeated (5 times) administrations of methamphetamine at 3-day intervals induced a sensitization to its ambulation-increasing effect, and the sensitization was significantly inhibited by 3-h pretreatment with either sulpiride (10-100 mg kg-1), or combined treatment with either sulpiride (3 or 10 mg kg-1) or nemonapride (0.01 or 0.03 mg kg-1) at each methamphetamine administration. Although the ambulation-increasing effect of methamphetamine disappeared by 3 h after the administration, the 3-h post-treatment with sulpiride (3 mg kg-1) or nemonapride (0.03 mg kg-1) after each methamphetamine administration was effective for a significant inhibition of the induction of methamphetamine sensitization, whereas, the comparatively higher doses of sulpiride (30 and 100 mg kg-1 in the combined treatment, and 10-100 mg kg-1 in the post-treatment) did not inhibit the methamphetamine sensitization. On the other hand, the repeated administrations of sulpiride (30 and 100 mg kg-1) alone, but not any doses of nemonapride, at 3-day intervals elicited a significant increase in the sensitivity to methamphetamine. These results suggest that, although the potencies of the anti-methamphetamine effects of sulpiride and nemonapride differ by a factor of 3000, they inhibit the induction of sensitization to methamphetamine in the pretreatment, combined treatment and early post-treatment schedules. However, it is also suggested that the repeated treatment with comparatively higher doses of sulpiride may produce a denervation supersensitivity of dopamine D2 receptors, and resultant increase in the sensitivity to methamphetamine.
authors: Department of Neurobiology and Behavior, Gunma University School of Medicine, Maebashi, Japan.
authors: H
authors: H
authors: Kuribara
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001549:Benzamides; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D008694:Methamphetamine; D013469:Sulpiride; C030265:nemonapride