Chronic SCH 23390 produces tolerance to morphine extrapyramidal effects.
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Biomedical subjects
Publications and source records attributed to P Devoto.
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D-Ala2, D-Leu5-enkephalin (DADLE) and dynorphin1-13 (Dyn1-13) inhibited striatal adenylate cyclase activity, both basal and dopamine-stimulated (DA), in rats and guinea pigs. The kappa-agonists bremazocine (BRZ), U-50,488 (trans-3,4-dicloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide), and U-69,593 (5 alpha, 7 alpha 8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl-1-oxaspiro (4.5)dec-8yl) benzeneacetamide inhibited only the basal adenylate cyclase activity, and such an effect was restricted to guinea pig striatum, an area known to contain a high density of kappa-binding sites. Moreover, BRZ was found to antagonize the inhibitory effect of both DADLE and Dyn1-13 in rat striatum.
In mice lefetamine, at the dose of 50 mg/kg produces motor hyperactivity and at the dose of 60 mg/kg produces analgesia. Both effects are abolished by naloxone. Displacement studies by using [3H]-Naloxone (Nx), [3H]-D-Ala-Met-Enkephalinamide (DAMA) and [3H]-Ethylketocyclazocine (EKC) showed that lefetamine competes with all these opiates with an affinity 50 times lower than that of morphine. The displacing capacity of lefetamine is decreased in the presence of 50 mM Na+. It is concluded that lefetamine is an opioid agonist.
Female rats were made dependent to high doses of morphine (400 mg/kg per day) or methadone (60-80 mg/kg per day) and subsequently exposed to adult males. None of the morphine-dependent rats became pregnant while there were no differences in the gestation time and number of young in the litter born to each rat in the methadone and the control groups. The values for muscarinic, serotonergic and opiate receptors measured in the whole brain of the offspring at 1 and 7 days after birth were similar in the control and in the methadone-exposed animals. Brain beta-receptors were lower in rats exposed in utero to methadone at 1 and 7 days. [3H]IMI binding sites were steadily and significantly lower in the whole brain of rats born to methadone-dependent animals than in the brain of controls. In 2 month old animals, the decrease of [3H]IMI binding capacity was associated with a decrease of [3H]5HT uptake. In the light of these findings the authors propose a unifying hypothesis to explain the altered reactivity to morphine of animals treated with opiates during gestation.
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Sulpiride and other benzamides' displacement of [3H]-spiroperidol binding to rat and dog anterior pituitary dopaminergic receptors was found to be selectively sodium dependent, while typical neuroleptic activity was not influenced by NaCl. These results indicate the existence in the anterior pituitary of a subpopulation of dopaminergic receptors with which benzamides interact.
Sulpiride and other benzamide (BM)-displacing activity on [3H]-spiroperidol ([3H]SPIR) binding by rat striatal dopaminergic receptors was found to be uniquely sodium-dependent, while classical neuroleptic (NL) activity was not influenced by NaCl. These results suggest the existence of at least two populations of striatal dopaminergic receptors, sodium-dependent and sodium-independent, through which BM and NL respectively interact.
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Ethanol-naive Sardinian alcohol-preferring (sP) and Sardinian alcohol-non-preferring (sNP) rats were tested to evaluate the levels of serotonin (5-HT) and 5-hydroxyindol-3-yl-acetic acid (5-HIAA) in the frontal cortex, hypothalamus, and nucleus accumbens, and the levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hypothalamus and nucleus accumbens. Compared with the sNP line, the sP rats had lower 5-HT and 5-HIAA concentrations in the frontal cortex, whereas no differences were found in the other brain areas tested, neither for neurotransmitters nor their metabolites. As the decreased 5-HT function is a feature shared by different alcohol-preferring strains, it could be linked to the genetic predisposition to voluntary ethanol consumption.