Biomaterial Database

Chronic administration of haloperidol and clozapine induces differential effects on the expression of Arc and c-Fos in rat brain. 2014

Cheryl M Collins, and Martyn D Wood, and J Martin Elliott

Leicester School of Pharmacy, De Montfort University, Leicester, UK Current address: Loxbridge Research, Royal Free Hampstead NHS Trust, London, UK.

The modulation of genes implicated in synaptic plasticity following administration of antipsychotic drugs has been instrumental in understanding their possible mode of action. Arc (Arg 3.1) is one such gene closely associated with changes in synaptic plasticity. In this study we have investigated the changes in expression of Arc protein following acute and chronic administration of a typical antipsychotic (haloperidol) and an atypical antipsychotic (clozapine) by means of immunohistochemistry compared to the prototypic gene marker c-Fos. In dorsal striatum haloperidol (1 mg/kg) significantly increased Arc expression following both acute and chronic (21 day) administration with evidence of modulation in induction after repeated dosing. No significant changes were observed following either acute or chronic administration of clozapine (20 mg/kg). In the nucleus accumbens shell both clozapine and haloperidol induced Arc expression following acute administration, again with evidence of modulation after chronic dosing. The pattern of induction of Arc expression following haloperidol and clozapine in both dorsal and ventral striatum was similar to that for c-Fos. In medial prefrontal and cingulate cortex, Arc expression was significantly decreased by clozapine but not haloperidol without any indication of modulation following chronic dosing, whereas no significant changes in c-Fos expression were observed with either drug. Since synaptic modulation mediated by Arc is associated with down-regulation of the AMPA glutamate receptor, this study suggests a mechanism whereby enhanced glutamate receptor efficacy in medial cortical areas may be a component of antipsychotic drug action.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009714	Nucleus Accumbens	Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.	Accumbens Nucleus,Nucleus Accumbens Septi,Accumbens Septi, Nucleus,Accumbens Septus, Nucleus,Accumbens, Nucleus,Nucleus Accumbens Septus,Nucleus, Accumbens,Septi, Nucleus Accumbens,Septus, Nucleus Accumbens
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
D003024	Clozapine	A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.	Clozaril,Leponex
D003342	Corpus Striatum	Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.	Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D003598	Cytoskeletal Proteins	Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.	Proteins, Cytoskeletal
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006179	Gyrus Cinguli	One of the convolutions on the medial surface of the CEREBRAL HEMISPHERES. It surrounds the rostral part of the brain and CORPUS CALLOSUM and forms part of the LIMBIC SYSTEM.	Anterior Cingulate Gyrus,Brodmann Area 23,Brodmann Area 24,Brodmann Area 26,Brodmann Area 29,Brodmann Area 30,Brodmann Area 31,Brodmann Area 32,Brodmann Area 33,Brodmann's Area 23,Brodmann's Area 24,Brodmann's Area 26,Brodmann's Area 29,Brodmann's Area 30,Brodmann's Area 31,Brodmann's Area 32,Brodmann's Area 33,Cingulate Gyrus,Gyrus Cinguli Anterior,Retrosplenial Complex,Retrosplenial Cortex,Anterior Cingulate,Anterior Cingulate Cortex,Cingular Gyrus,Cingulate Area,Cingulate Body,Cingulate Cortex,Cingulate Region,Gyrus, Cingulate,Posterior Cingulate,Posterior Cingulate Cortex,Posterior Cingulate Gyri,Posterior Cingulate Gyrus,Posterior Cingulate Region,Superior Mesial Regions,24, Brodmann Area,Anterior Cingulate Cortices,Anterior Cingulates,Anterior, Gyrus Cinguli,Anteriors, Gyrus Cinguli,Area 23, Brodmann,Area 23, Brodmann's,Area 24, Brodmann,Area 24, Brodmann's,Area 26, Brodmann,Area 26, Brodmann's,Area 29, Brodmann,Area 29, Brodmann's,Area 30, Brodmann,Area 30, Brodmann's,Area 31, Brodmann,Area 31, Brodmann's,Area 32, Brodmann,Area 32, Brodmann's,Area 33, Brodmann,Area 33, Brodmann's,Area, Cingulate,Body, Cingulate,Brodmanns Area 23,Brodmanns Area 24,Brodmanns Area 26,Brodmanns Area 29,Brodmanns Area 30,Brodmanns Area 31,Brodmanns Area 32,Brodmanns Area 33,Cingulate Areas,Cingulate Bodies,Cingulate Cortex, Anterior,Cingulate Cortex, Posterior,Cingulate Gyrus, Anterior,Cingulate Gyrus, Posterior,Cingulate Region, Posterior,Cingulate Regions,Cingulate, Anterior,Cingulate, Posterior,Cinguli Anterior, Gyrus,Cinguli Anteriors, Gyrus,Complex, Retrosplenial,Cortex, Anterior Cingulate,Cortex, Cingulate,Cortex, Posterior Cingulate,Cortex, Retrosplenial,Gyrus Cinguli Anteriors,Gyrus, Anterior Cingulate,Gyrus, Cingular,Gyrus, Posterior Cingulate,Posterior Cingulate Cortices,Posterior Cingulate Regions,Posterior Cingulates,Region, Cingulate,Region, Posterior Cingulate,Retrosplenial Complices,Retrosplenial Cortices,Superior Mesial Region
D006220	Haloperidol	A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)	Haldol