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Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats
Journal article   Open access   Peer reviewed

Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats

Angelica P. Escobar, Marcela P. Gonzalez, Rodrigo C. Meza, Veronica Noches, Pablo Henny, Katia Gysling, Rodrigo A. Espana, Jose A. Fuentealba and Maria E. Andres
The international journal of neuropsychopharmacology, v 20(8), pp 660-669
01 Aug 2017
DOI: https://doi.org/10.1093/ijnp/pyx042
PMID: 28531297
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1093/ijnp/pyx042View
Published, Version of Record (VoR)CC BY-NC V4.0,  Open

Abstract

Clinical Neurology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Pharmacology & Pharmacy Psychiatry Science & Technology
Background: Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of quinpirole, a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist. The mechanism underlying kappa opioid receptor potentiation of quinpirole-induced locomotor sensitization remains to be elucidated. Methods: Immunofluorescence anatomical studies were undertaken in mice brain slices and rat presynaptic synaptosomes to reveal kappa opioid receptor and D2R pre- and postsynaptic colocalization in the nucleus accumbens. Tonic and phasic dopamine release in the nucleus accumbens of rats repeatedly treated with U69593 and quinpirole was assessed by microdialysis and fast scan cyclic voltammetry. Results: Anatomical data show that kappa opioid receptor and D2R colocalize postsynaptically in medium spiny neurons of the nucleus accumbens and the highest presynaptic colocalization occurs on the same dopamine terminals. Significantly reduced dopamine levels were observed in quinpirole, and U69593-quinpirole treated rats, explaining sensitization of D2R. Presynaptic inhibition induced by kappa opioid receptor and D2R of electrically evoked dopamine release was faster in U69593-quinpirole compared with quinpirole-repeatedly treated rats. Conclusions: Pre- and postsynaptic colocalization of kappa opioid receptor and D2R supports a role for kappa opioid receptor potentiating both the D2R inhibitory autoreceptor function and the inhibitory action of D2R on efferent medium spiny neurons. Kappa opioid receptor co-activation accelerates D2R sensitization by contributing to decrease dopamine release in the nucleus accumbens.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Clinical Neurology
Neurosciences
Pharmacology & Pharmacy
Psychiatry
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