The effect of neurotensin, TRH and the delta-opioid receptor antagonist ICI 174864 on alcohol-induced narcosis in rats. 1987

P S Widdowson
Anglo-European College of Chiropractic, Bournemouth, Dorset, U.K.

The effects of microinjections of thyrotropin-releasing hormone (TRH), neurotensin and ICI 174864 into the nucleus accumbens, nucleus caudatus, septum and mesencephalic periaqueductal grey were studied on ethanol-induced narcosis in the rat. Levels of narcosis were assessed by alterations in ethanol-induced hypothermia and sleep time. Ethanol produces a 2 degree C fall in body temperature over the first hour which then recovered over the next 2 h. Sedation was produced to the extent that the righting reflex was lost for between 80 and 90 min. In the nucleus caudatus all 3 peptides were ineffective at altering narcosis. In the periaqueductal grey, septum and accumbens, TRH (5 micrograms) and ICI 174864 (1 microgram) microinjections significantly reduced the sleep time by between 50 and 70%. ICI 174864 was approximately 10 times more potent that TRH at reducing the sleep time. In addition, both these peptides significantly accelerated the recovery from the ethanol-induced hypothermia in the periaqueductal grey, septum and accumbens. ICI 174864 prevented the ethanol-induced fall in body temperature. Neurotensin (5 micrograms) significantly increased the sleep time by up to 50% and potentiated the ethanol-induced hypothermia. These results suggest that the administration of TRH or the blockade of delta-opioid receptors, resulting in an inhibition of endogenous enkephalin transmission, may significantly inhibit ethanol narcosis in the rat. Opposing this, the application of neurotensin appears to potentiate ethanol narcosis. These results also indicate that endogenous enkephalin release plays an important role in ethanol narcosis.

UI MeSH Term Description Entries
D008297 Male Males
D009496 Neurotensin A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter.
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
D011957 Receptors, Opioid Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D012007 Rectum The distal segment of the LARGE INTESTINE, between the SIGMOID COLON and the ANAL CANAL. Rectums
D001831 Body Temperature The measure of the level of heat of a human or animal. Organ Temperature,Body Temperatures,Organ Temperatures,Temperature, Body,Temperature, Organ,Temperatures, Body,Temperatures, Organ
D002493 Central Nervous System Diseases Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. CNS Disease,Central Nervous System Disease,Central Nervous System Disorder,CNS Diseases,Central Nervous System Disorders
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
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
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

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