We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Differential effects of olanzapine at dopamine D[sub 1] and D[sub 2] receptors in dopamine depleted animals.
- Authors
Ninan, I.; Kulkarni, S. K.
- Abstract
Abstract The aim of the present study was to investigate the locomotor stimulant effects of the atypical antipsychotic agent, olanzapine, in mice depleted of their dopamine by reserpine and alpha-methyl-DL-p-tyrosine pretreatment. Olanzapine (0.5, 1 and 2 mg/kg) dose-dependently increased locomotor activity, which was completely blocked by the selective dopamine D[sub 2] receptor antagonist, pimozide (0.5 mg/kg) but not by selective dopamine D[sub 1] receptor antagonist, SCH 23390 (0.5 and 1 mg/kg). Unlike olanzapine, the selective dopamine D[sub 2] receptor antagonists such as haloperidol (0.25 and 0.5 mg/kg) and pimozide (0.5 and 1 mg/kg), the selective 5-HT[sub 2A] receptor antagonist, ritanserin (0.5 and 1 mg/kg) or the antimuscarinic agent scopolamine (0.5 and 1 mg/kg) failed to produce any locomotor stimulant effect. Olanzapine (1 and 2 mg/kg) and SCH 23390 (0.5 and 1 mg/kg) blocked hyperlocomotion and stereotypy induced by the selective dopamine D[sub 1] receptor agonist, SKF 38393 (10 and 25 mg/kg). Olanzapine (1 and 2 mg/kg) blocked hyperlocomotion and stereotypy induced by B-HT 920 (1 and 2 mg/kg), a selective dopamine D[sub 2] receptor agonist, whereas it blocked the hyperlocomotion but not stereotypy induced by the non-selective dopamine receptor agonist, apomorphine (0.5 and 1 mg/kg). The higher dose (4 mg/kg) of olanzapine blocked both stereotypy and hyperlocomotion induced by apomorphine. Olanzapine, in mice depleted of their dopamine stores, exhibited properties consistent with those of a D[sub 2] partial agonist having strong D[sub 1] antagonist property. The atypical nature of its clinical effect may be explained by a dual effect, partial agonistic-like action at D[sub 2] receptors and antagonist-like activity at D[sub 1] receptors, respectively.
- Subjects
OLANZAPINE; DOPAMINE receptors; STIMULANTS; BIOCHEMICAL mechanism of action; THERAPEUTICS
- Publication
Psychopharmacology, 1999, Vol 142, Issue 2, p175
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s002130050877