Kappa opioid inhibition of morphine and cocaine self-administration in rats

doi:10.1016/0006-8993(95)00306-B

Brain Research

Volume 681, Issues 1–2, 29 May 1995, Pages 147-152

https://doi.org/10.1016/0006-8993(95)00306-B Get rights and content

Abstract

Two kappa agonists, U50,488 and spiradoline, produced dose-related acute decreases in both morphine and cocaine self-administration in rats; higher doses of both agents were required to decrease rates of bar-pressing for water. On the day after kappa agonist administration, both agents produced extinction-like patterns of responding in many rats self-administering morphine or cocaine but not in rats responding for water. Two days after their administration, both U50,488 and spiradoline produced significant decreases in both morphine and cocaine intake; some rats continued to show decreases in drug self-administration for 5–6 days. Although the kappa antagonist nor-binaltorphimine (10 mg/kg s.c.) had no effect itself on either morphine or coccaine self-administration, it fully antagonized the effects of U50,488 (10 m/kg i.p.). The results suggest that although endogenous kappa opioid systems may not tonically modulate mechanisms involved in drug reinforcement, pharmacological activation of kappa pathways may be a novel and effective pharmacological approach to treating both opioid and stimulant addiction.

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Kappa opioid inhibition of morphine and cocaine self-administration in rats

Abstract

Neuropharmacology

Neurosci. Lett.

Jap. J. Pharmacol.

The kappa-opioid U-50,488H suppresses the initiation of nocturnal spontaneous drinking in normally hydrated rats

Psychopharmacology

Evidence that the aversive effects of opioid antagonists and κ-agonists are centrally mediated

Psychopharmacology

Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies

J. Pharmacol. Exp. Ther.

Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats

Blockade of morphine reward through the activation of κ-opioid receptors in mice

Neuropharmacology

Changes in morphine self-administration after brainstem lesions in rats

Psychopharmacology