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• W1586540336 abstract "Repeated cocaine exposure upregulates κ opioids and their receptors in the mesocorticolimbic system; the ensuing κ-mediated dysphoria appears to contribute to addiction and withdrawal. As a potential rehabilitation strategy to reverse cocaine-induced κ sensitization, the present study used tritiated dopamine release assays to examine the induction of κ-opioid tolerance in cultured mesencephalic neurons. Administration of the κ agonist U69,593 inhibited tetrodotoxin-sensitive, spontaneous (EC 50 = 1.5 n m ), and potassium-stimulated (EC 50 = 10 n m ) release. These effects were blocked by pertussis toxin and by the κ antagonist nor-binaltorphimine. The 2 d agonist exposure (1 μ m ) caused a shift in the U69,593 dose–response curve that was greater in the potassium-stimulated paradigm (140-fold) than in the spontaneous release assay (sixfold). These results were attributable to the attenuation of κ-receptor signaling mechanisms and to dependence. In the stimulated release assay, attenuation of κ signaling caused by 4 hr of U69,593 exposure recovered with a half-life of 1.1 hr, whereas attenuation after 144 hr of exposure recovered slowly ( t ½ = 20 hr). In the spontaneous release assay, attenuation of κ-opioid signaling occurred slowly ( t ½ = 22 hr), and resensitization after a 144 hr exposure was rapid ( t ½ < 1 hr). κ-Opioid dependence was observed after 144 hr of U69,593 exposure. Thus multiple mechanisms of adaptation to κ-opioid exposure occur in mesocorticolimbic neurons. These data support the idea that the administration of κ opioids might facilitate drug rehabilitation." @default.
• W1586540336 created "2016-06-24" @default.
• W1586540336 creator A5061898512 @default.
• W1586540336 creator A5082371543 @default.
• W1586540336 date "1999-07-15" @default.
• W1586540336 modified "2023-10-17" @default.
• W1586540336 title "κ-Opioid Tolerance and Dependence in Cultures of Dopaminergic Midbrain Neurons" @default.
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• W1586540336 doi "https://doi.org/10.1523/jneurosci.19-14-05750.1999" @default.
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