European Journal of Neuroscience 2009-08-01

Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking.

Rachel J Smith, Ronald E See, Gary Aston-Jones

Index: Eur. J. Neurosci. 30 , 493-503, (2009)

Full Text: HTML

Abstract

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 of cue-induced reinstatement. These results show that orexin transmission at the orexin 1 receptor, but not the orexin 2 receptor, is necessary for the reinstatement of cocaine-seeking elicited by drug-paired cues and that orexin signaling is not critical for cocaine reinforcement or cocaine-stimulus conditioning.


Related Compounds

Related Articles:

Niemann-pick C1 is essential for ebolavirus replication and pathogenesis in vivo.

2015-01-01

[MBio 6 , e00565-15, (2015)]

SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells.

2015-11-10

[Oncotarget 6 , 37410-25, (2015)]

Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice.

2015-09-05

[Mol. Cell. Endocrinol. 412 , 12-8, (2015)]

Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus.

2014-11-12

[J. Neurosci. 34(46) , 15306-18, (2014)]

Experience-dependent DNA methylation regulates plasticity in the developing visual cortex.

2015-07-01

[Nat. Neurosci. 18 , 956-8, (2015)]

More Articles...