EFFECT OF CHRONIC TREATMENT WITH NNC 756, A NEW D-1 RECEPTOR ANTAGONIST, OR RACLOPRIDE, A D-2 RECEPTOR ANTAGONIST, IN DRUG-NAIVE CEBUS MONKEYS - DYSTONIA, DYSKINESIA AND D-1/D-2 SUPERSENSITIVITY

被引:22
作者
GERLACH, J
HANSEN, L
机构
[1] St Hans Hospital, Dept. P, Research Institute of Biological Psychiatry, Roskilde
关键词
D-1 DOPAMINE ANTAGONISTS; D-2 DOPAMINE ANTAGONISTS; NNC; 756; RACLOPRIDE; DYSTONIA; DYSKINESIA; DOPAMINE SUPERSENSITIVITY; MONKEY;
D O I
10.1177/026988119300700407
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
When given subcutaneously in gradually increasing doses, up to 1 mg/kg, NNC 756, a dopamine (DA) D-l antagonist, failed to produce dystonia in eight drug-naive Cebus monkeys. In contrast, raclopride, a DA D-2 antagonist, produced dystonia at low doses (0.010-0.015 mg/kg). Following pre-treatment with raclopride, NNC 756 also induced dystonia at low doses (0.015-0.025 mg/kg), but continued treatment caused tolerance, and increasing doses of NNC 756 could be administered without induction of dystonia. NNC 756 induced a dose-dependent parkinsonism (slow, stiff movements and tremor), and more sedation than raclopride. After treatment for 14 weeks, withdrawal of raclopride (0.01 mg/kg) led to mild oral dyskinesia (tardive dyskinesia), while withdrawal of NNC 756 (1.0 mg/kg) led to a special grooming syndrome, but no dyskinesia. Withdrawal of raclopride as well as NNC 756 led to behavioural D-l and D-2 dopamine supersensitivity in the form of increased dyskinesia (including grooming after NNC 756) induced by D-l agonist (SKF 81297) and increased arousal induced by D-2 agonist (quinpirole). These results indicate that D-l antagonists such as NNC 756 elicit fewer extrapyramidal symptoms (both acute and tardive) than D-2 antagonists such as raclopride, although extremely high doses may cause a special grooming withdrawal syndrome.
引用
收藏
页码:355 / 364
页数:10
相关论文
共 26 条
[1]   NNC-112, NNC-687 AND NNC-756, NEW SELECTIVE AND HIGHLY POTENT DOPAMINE D1 RECEPTOR ANTAGONISTS [J].
ANDERSEN, PH ;
GRONVALD, FC ;
HOHLWEG, R ;
HANSEN, LB ;
GUDDAL, E ;
BRAESTRUP, C ;
NIELSEN, EB .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 219 (01) :45-52
[2]   DOPAMINE-D1 (SCH-23390) AND DOPAMINE-D2 (HALOPERIDOL) ANTAGONISTS IN DRUG-NAIVE MONKEYS [J].
CASEY, DE .
PSYCHOPHARMACOLOGY, 1992, 107 (01) :18-22
[3]  
CASEY DE, 1991, J EUR COLL NEUROPS S, V15, P351
[4]  
CHIPKIN RE, 1988, J PHARMACOL EXP THER, V247, P1093
[5]  
Christensen A.V., 1990, BEHAV NEUROL, V3, P49
[6]  
COFFIN VL, 1989, J PHARMACOL EXP THER, V249, P769
[7]  
COFFIN VL, 1991, 30TH ANN M AM COLL N
[8]   D-1-DOPAMINE RECEPTORS AND THE TOPOGRAPHY OF UNCONDITIONED MOTOR BEHAVIOR - STUDIES WITH THE SELECTIVE, FULL EFFICACY BENZAZEPINE D-1-AGONIST SKF-83189 [J].
DALY, SA ;
WADDINGTON, JL .
JOURNAL OF PSYCHOPHARMACOLOGY, 1992, 6 (01) :50-60
[9]   SCH-23390 DISSOCIATED FROM CONVENTIONAL NEUROLEPTICS IN APOMORPHINE CLIMBING AND PRIMATE ACUTE DYSKINESIA MODELS [J].
GERHARDT, S ;
GERBER, R ;
LIEBMAN, JM .
LIFE SCIENCES, 1985, 37 (25) :2355-2363
[10]  
Gerlach J., 1991, BIOL PSYCHIAT, V1, P609