D3 receptors and the actions of neuroleptics in the ventral striatopallidal system of schizophrenics
D3 receptors and the actions of neuroleptics in the ventral striatopallidal system of schizophrenics
复制标题
DOI：
10.1111/j.1749-6632.1999.tb09291.x
复制
发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Gurevich, EV
中科院分区：
文献类型：
--
作者：
Joyce, JN;Gurevich, EV
The mesolimbic dopamine (DA) system and an important target receptor, the D-3 receptor, have been implicated in schizophrenia. We have identified, using non-radioactive in situ hybridization histochemistry, that D-3 mRNA-positive neurons are highly concentrated in the ventral striatum, efferents of the ventral striatum (globus pallidus internal, ventral palladium, substantia nigra pars reticulata), and in regions projecting to the ventral striatum (medial dorsal thalamus, nucleus basalis, extended amygdala). DQ receptors are also highly enriched in the "limbic" striatal-pallidal-thalamic loop, exhibiting segregation from the D-2 receptor-enriched "motor loop." This supports data developed in rats showing that the D-3 receptor is a target of the mesolimbic DA system that can modulate the limbic striato-palladial-thalamic Loop. However, D-2 and D-3 receptors and their mRNAs are co-localized in many sensory regions (lateral and medial geniculate nuclei, basolateral and basomedial amygdala, regions of thalamus), suggesting mechanisms of cross-talk, We have also demonstrated that there are 35% elevations in D-3 receptor number in ventral striatal neurons and their striatopalladial targets in schizophrenics that is reduced by concurrent antipsychotic treatment. Chronic haloperidol treatment to rats for 6 months with a 2-month withdrawal does not result in elevated D-3 receptor number. We hypothesize that antipsychotic treatment via D-3 receptors returns balance to limbic efferents of the ventral striatum. We established that early neonatal damage to the nigrostriatal DA system in rats produces characteristic adaptations in the pre- and post-synaptic components of the mesolimbic DA system that can provide a model to explore regulation by antipsychotics. This includes elevated release of DA from the mesolimbic DA terminals, elevated D-3 receptor mRNA in the Islands of Calleja and nucleus accumbens, and enhanced behavioral response to psychostimulants.
