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  • 1
    ISSN: 1432-2072
    Keywords: Conditioned suppression of motility ; Antidepressant-like effects ; Enkephalin-degrading enzymes ; RB 101 ; L-365,260 ; BC 264 ; L-364,718 ; δ-Opioid receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Systemic administration of RB 101, a complete inhibitor of the enkephalin degrading enzymes, has been reported to induce naltrindole-reversed anti-depressant-like effects in the conditioned suppression of motility (CSM) test in mice. The selective CCKB antagonist L-365,260 also elicits the same naltrindole-blocked responses on CSM. The aim of this study was therefore to investigate the possible modulation of RB 101 induced behavioral responses by activation or blockade of CCK receptors. Thus, the effects induced by RB 101 administered alone or associated with an ineffective dose of a selective CCKB agonist (BC 264), a CCKB antagonist (L-365,260) or a CCKA antagonist (L-364,718), were evaluated on the CSM in mice. RB 101 alone decreased the stress-induced loss of motility, as previously reported. The antidepressant-like effect of RB 101 was potentiated by L-365,260, and suppressed by BC 264 and to a lesser extent by L-364,718. The facilitatory effect induced by L-365,260 on RB 101 responses was blocked by the delta selective antagonist naltrindole. All these effects occurred only in shocked animals. The present results suggest that the activation of CCKA and CCKB receptors by endogenous CCK, could play an opposite role in the control of behavioral responses induced by endogenous enkephalins. Delta opioid receptors seem to be selectively involved in this interaction.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Key words Protein kinases ; Tyrosine kinase inhibitor ; Serine/threonine kinase inhibitor ; Locus coeruleus ; Periaqueductal gray matter ; Morphine withdrawal ; Naloxone.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this study was to evaluate the role played in the behavioral expression of morphine withdrawal syndrome by protein kinases in the locus coeruleus and the periaqueductal gray matter. Two different families of specific protein kinases have been investigated: serine/threonine and tyrosine kinases. Rats were implanted with cannulas into both the lateral ventricle and the locus coeruleus or the periaqueductal gray matter. Physical dependence was induced by chronic peripheral administration of morphine (from 7 to 30 mg/kg) and withdrawal syndrome was precipitated by injection of naloxone (2 μg) into the lateral ventricle. The administration of the serine/threonine kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, H7 (1, 3, 10, and 30 nmol per side) into the locus coeruleus induced a strong attenuation of morphine withdrawal behavior. Signs related to the motor component of abstinence, such as jumping, rearing, and hyperactivity, were the most severely reduced. However, this effect was not dose-dependent, and the response was almost the same with all the doses used. A similar attenuation was observed after the injection of H7 (1, 3, and 10 nmol per side) into the periaqueductal gray matter, but in this case motor signs were less strongly reduced and a larger number of signs were modified, mainly when using the highest dose. The administration of the tyrosine kinase inhibitor 2-hydroxy-5-[N-[(2,5-dihydroxyphenyl)methyl] amino]-benzoic acid 3-phenylpropyl ester, KB23 (0.3, 1, and 3 nmol per side) into the locus coeruleus or the periaqueductal gray matter had no effect on the withdrawal syndrome behavior, except on teeth chattering. These results suggest that, in the locus coeruleus and in the periaqueductal gray matter, serine/threonine kinases are implicated in the behavioral expression of morphine abstinence. In these brain structures, tyrosine kinases appear not to be involved.
    Type of Medium: Electronic Resource
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