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BEHAVIORAL NEUROSCIENCE Orexin/hypocretin signaling at the orexin 1 receptor

Orexin/hypocretin signaling at the orexin 1 receptor
regulates cue-elicited cocaine-seeking
Rachel J. Smith, Ronald E. See and Gary Aston-Jones
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, 403 Basic Science Building, Charleston,
SC 29425-5100, USA
Keywords: addiction, hypothalamus, rat, reinstatement, relapse, self-administration
The orexin / hypocretin system has recently been implicated in reward-processing and addiction. We examined the involvement of the
orexin system in cue-induced reinstatement of extinguished cocaine-seeking by administering the orexin 1 receptor antagonist SB-
334867 (SB) or the orexin 2 receptor antagonist 4-pyridylmethyl (S)-tert-leucyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (4PT)
prior to reinstatement testing. Male Sprague Dawley rats self-administered cocaine in 2-h sessions for 10 days, followed by extinction
training. Reinstatement of cocaine-seeking was elicited by presentation of tone + light cues previously paired with cocaine infusions.
SB (10, 20 and 30 mg / kg) dose-dependently decreased cue-induced reinstatement of cocaine-seeking without significantly affecting
responding during late extinction. 4PT (10 and 30 mg / kg) did not significantly alter cue-induced reinstatement. In separate
experiments, the highest doses of SB and 4PT had no significant effect on established cocaine self-administration, and 4PT reduced
spontaneous activity in a locomotor test to a greater extent than SB. Finally, SB (30 mg / kg) had no effect on the acquisition of
cocaine-paired cues during a Pavlovian cocaine-stimulus conditioning session in the operant chamber. Pretreatment with SB prior to
the Pavlovian acquisition session had no effect on subsequent cue-induced reinstatement of cocaine-seeking elicited by those cues.
However, pretreatment with SB prior to a second reinstatement session in the same animals significantly attenuated the expression


Source: Aston-Jones, Gary - Department of Neurosciences, Medical University of South Carolina


Collections: Biology and Medicine