Chronic treatment with chlorpromazine, thioridazine or haloperidol increases striatal enkephalins and their release from rat brain. 1991

Z S Herman, and M Huzarska, and K Kmieciak-Kolada, and J Kowalski
Department of Clinical Pharmacology, Silesian School of Medicine, Katowice, Poland.

The aim of this paper is to study the effect of 1, 2 or 3 months' administration of chlorpromazine (CPZ), thioridazine (TDZ) (2 or 6 mg/kg) or haloperidol (HAL) (0.25 or 1 mg/kg) IP on the level of leu- and met-enkephalin (ENK) in striatum. A dose- and time-dependent increase of striatal ENK level was observed after chronic administration of the neuroleptics (NL), but 8 days after withdrawal of chronically administered NL striatal ENK was decreased. Apomorphine pretreatment significantly attenuated the elevation in ENK produced by chronic injections of NL. In perfusion fluid obtained from the lateral ventricle of animals treated 1 month with HAL a dose-dependent increase of ENK levels was observed, which was augmented by potassium ions. It is concluded that: 1) Chronic administration of neuroleptic drugs that block dopamine receptors increases the level and the release of striatal enkephalins; 2) The results support the hypothesis that activation of dopaminergic neurons tonically inhibits the synthesis of enkephalins in the striatum.

UI MeSH Term Description Entries
D008297 Male Males
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D002746 Chlorpromazine The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. Aminazine,Chlorazine,Chlordelazine,Chlorpromazine Hydrochloride,Contomin,Fenactil,Largactil,Propaphenin,Thorazine,Hydrochloride, Chlorpromazine
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
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004743 Enkephalin, Leucine One of the endogenous pentapeptides with morphine-like activity. It differs from MET-ENKEPHALIN in the LEUCINE at position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN. Leucine Enkephalin,5-Leucine Enkephalin,Leu(5)-Enkephalin,Leu-Enkephalin,5 Leucine Enkephalin,Enkephalin, 5-Leucine,Leu Enkephalin
D004744 Enkephalin, Methionine One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN. Methionine Enkephalin,5-Methionine Enkephalin,Met(5)-Enkephalin,Met-Enkephalin,5 Methionine Enkephalin,Enkephalin, 5-Methionine,Met Enkephalin
D004745 Enkephalins One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. Enkephalin
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

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