Biomaterial Database

Expression of noradrenergic alpha1, serotoninergic 5HT2a and dopaminergic D2 receptors on neurons activated by typical and atypical antipsychotic drugs. 2006

Jianyi Ma, and Nancy Ye, and Bruce M Cohen

Molecular Pharmacology Laboratory Mailman Research Center, McLean Hospital Belmont, 115 Mill Street, Belmont, MA 02478, USA.

Antipsychotic agents produce activation of a subset of largely dynorphinergic/GABAergic neurons in the shell of nucleus accumbens (AcbShB), central amygdaloid nucleus (CeA) and midline thalamic central medial nucleus (CM) in rats. It is not known why these particular neurons respond to antipsychotic drugs. The present study tested the hypothesis that activated neurons bear subtypes of monoamine receptors to which antipsychotic drug are known to bind, including dopaminergic D2, serotoninergic 5HT2a and noradrenergic alpha1 receptors. Rats were treated with the typical antipsychotic haloperidol or the atypical antipsychotic clozapine. Double immunofluorescence labeling was performed with antibodies directed against (1) the expression of Fos proteins, indicating drug-induced cell activation, and (2) each of the monoamine receptor proteins noted. All three receptors examined were expressed in haloperidol- and clozapine-activated neurons in AcbSh. Furthermore, noradrenergic alpha1 receptors were extensively expressed in activated neurons in CeA and CM, as well. The results suggest that bearing monoamine receptors with high binding affinity for typical and/or atypical antipsychotic drugs might be a key feature of neurons which respond to these drugs. In AcbSh, activated neurons appeared to bear each receptor and, therefore, it is possible that not only the individual but also the combined effect of antipsychotic drugs at multiple receptors may explain why they directly activate certain cells and not others. Also, bearing noradrenergic alpha1 receptor neurons was a shared feature of all activated cells in each location tested, suggesting inhibition of noradrenergic alpha1 receptors may contribute to antipsychotic drug action at these sites.

UI	MeSH Term	Description	Entries
D007150	Immunohistochemistry	Histochemical localization of immunoreactive substances using labeled antibodies as reagents.	Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014150	Antipsychotic Agents	Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.	Antipsychotic,Antipsychotic Agent,Antipsychotic Drug,Antipsychotic Medication,Major Tranquilizer,Neuroleptic,Neuroleptic Agent,Neuroleptic Drug,Neuroleptics,Tranquilizing Agents, Major,Antipsychotic Drugs,Antipsychotic Effect,Antipsychotic Effects,Antipsychotics,Major Tranquilizers,Neuroleptic Agents,Neuroleptic Drugs,Tranquillizing Agents, Major,Agent, Antipsychotic,Agent, Neuroleptic,Drug, Antipsychotic,Drug, Neuroleptic,Effect, Antipsychotic,Major Tranquilizing Agents,Major Tranquillizing Agents,Medication, Antipsychotic,Tranquilizer, Major
D015153	Blotting, Western	Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.	Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D015870	Gene Expression	The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.	Expression, Gene,Expressions, Gene,Gene Expressions
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017448	Receptors, Dopamine D2	A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.	Dopamine D2 Receptors,Dopamine-D2 Receptor,D2 Receptors, Dopamine,Dopamine D2 Receptor,Receptor, Dopamine-D2
D044402	Receptor, Serotonin, 5-HT2A	A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.	Serotonin 2A Receptor,5-HT(2A) Receptor,5-HT2A Receptor,Receptor, Serotonin 2A,Serotonin 2A Receptors,5 HT2A Receptor,Receptor, 5-HT2A,Receptors, Serotonin 2A