Blunted brain metabolic response to ketamine in mice lacking D(1A) dopamine receptors.
Brain Res
; 894(2): 167-80, 2001 Mar 16.
Article
in En
| MEDLINE
| ID: mdl-11251190
ABSTRACT
The interaction of glutamatergic and dopamine neurotransmission is thought to have relevance to both the pathophysiology and pharmacotherapy of schizophrenia. For example, subanesthetic doses of the N-methyl-D-aspartate receptor (NMDA-R) antagonist ketamine induce schizophrenia-like behavioral effects in humans and both behavioral and brain metabolic activation in rodents. Blockade of NMDA-R results in dopamine release, and antipsychotic drugs that block dopamine neurotransmission decrease NMDA-R antagonist-induced behavioral activation. The involvement of dopamine receptors in brain metabolic activation induced by ketamine is, however, unknown. The present study used D(1A) knockout mice to determine the role of dopamine D(1A) receptors in the effects of subanesthetic doses of ketamine on both behavioral responses and on alterations in regional [14C]2-deoxyglucose (2-DG) uptake. There was less ketamine-induced behavioral activation in D(1A) knockout mice than in wild-type mice. In wild-type mice, ketamine (30 mg/kg) induced dramatic increases in 2-DG uptake in limbic cortical regions, hippocampal formation, nucleus accumbens, basolateral amygdala, and caudal parts of the substantia nigra pars reticulata. D(1A) knockout mice exhibited blunted metabolic activation in response to ketamine in a neuroanatomically specific manner. The selective D(1) antagonist, SCH23390 (0.3 mg/kg), inhibited both ketamine-induced brain metabolic activation and behavioral responses in the wild-type mice, with a similar neuroanatomical specificity observed in the D(1A) knockout mice. Thus, the neuroanatomically selective role that D(1A) receptors play in ketamine-induced behavior and regional brain metabolic activation in mice provides a useful model for further studies of how the D(1A) receptor function may be altered in schizophrenia.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Receptors, Dopamine D1
/
Ketamine
/
Anesthetics, Dissociative
Limits:
Animals
Language:
En
Journal:
Brain Res
Year:
2001
Document type:
Article
Affiliation country:
United States