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2015 ; 6
(1
): 138-46
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Hypocretin/Orexin regulation of dopamine signaling and cocaine
self-administration is mediated predominantly by hypocretin receptor 1
#MMPMID25496218
Prince CD
; Rau AR
; Yorgason JT
; Espaņa RA
ACS Chem Neurosci
2015[Jan]; 6
(1
): 138-46
PMID25496218
show ga
Extensive evidence suggests that the hypocretins/orexins influence cocaine
reinforcement and dopamine signaling via actions at hypocretin receptor 1. By
comparison, the involvement of hypocretin receptor 2 in reward and reinforcement
processes has received relatively little attention. Thus, although there is some
evidence that hypocretin receptor 2 regulates intake of some drugs of abuse, it
is currently unclear to what extent hypocretin receptor 2 participates in the
regulation of dopamine signaling or cocaine self-administration, particularly
under high effort conditions. To address this, we examined the effects of
hypocretin receptor 1, and/or hypocretin receptor 2 blockade on dopamine
signaling and cocaine reinforcement. We used in vivo fast scan cyclic voltammetry
to test the effects of hypocretin antagonists on dopamine signaling in the
nucleus accumbens core and a progressive ratio schedule to examine the effects of
these antagonists on cocaine self-administration. Results demonstrate that
blockade of either hypocretin receptor 1 or both hypocretin receptor 1 and 2
significantly reduces the effects of cocaine on dopamine signaling and decreases
the motivation to take cocaine. In contrast, blockade of hypocretin receptor 2
alone had no significant effects on dopamine signaling or self-administration.
These findings suggest a differential involvement of the two hypocretin
receptors, with hypocretin receptor 1 appearing to be more involved than
hypocretin receptor 2 in the regulation of dopamine signaling and cocaine
self-administration. When considered with the existing literature, these data
support the hypothesis that hypocretins exert a permissive influence on dopamine
signaling and motivated behavior via preferential actions on hypocretin receptor
1.