Long-lasting effects of chronic μ-opioid intake on the signal transmission via dopamine D1receptors in the limbic forebrain of drug deprived rats

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Abstract

Rats orally self-administered the potent and selective μ-opioid receptor agonist etonitazene for 8 weeks (free choice between three opioid solutions and water resulting in low drug intake, or forced intake of a single drug solution resulting in high opioid consumption). The signal transmission in membranes of the limbic forebrain (nucleus accumbens and olfactory tubercle) was studied during acute withdrawal (2 days of abstinence) and after 6 weeks of drug deprivation. Binding experiments with the dopamine (DA) D1receptor antagonist [3H]SCH23390 revealed in the high consuming rats an increased binding density (B(max)) by 19% during withdrawal and a decreased B(max) by 17% after long-term abstinence compared with drug-naive controls (each P<0.05). The addition of 500 nM DA reduced the [3H]SCH23390 binding affinity (K(d) increased by 60-105%) and density (by 15-23%) in each of the five groups (P<0.001). During acute withdrawal, the portion of B(max) inhibited by DA increased by 83% in the high consuming rats vs. the controls (P<0.05). Full concentration-response curves of adenylyl cyclase (AC) stimulation by the DA D1receptor agonist dihydrexidine and of inhibition of forskolin stimulated AC activity by the GTP analogue guanosine-5'-O-(3-thio)triphosphate (GTPγS) were performed: the former revealed a reduced maximum efficacy (E(max) decreased by 23-37%, P<0.001), the latter a reduced effective concentration (EC50decreased by 60-103%, P<0.05), in each etonitazene-experienced group vs. the controls. Copyright (C) 1998 Elsevier Science Ltd.

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May, T., Juilfs, F., & Wolffgramm, J. (1998). Long-lasting effects of chronic μ-opioid intake on the signal transmission via dopamine D1receptors in the limbic forebrain of drug deprived rats. Neuropharmacology, 37(8), 997–1006. https://doi.org/10.1016/S0028-3908(98)00089-6

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