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| Paper IPM / Cognitive / 14878 |
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The orexin/hypocretin system has been implicated in motivation for drug reward and relapse. Orexin neurons of the hypothalamus send widespread axonal efferents to many reward-associated regions of the brain such as ventral pallidum (VP). Several studies have investigated the involvement of orexin signaling in motivation for cocaine, but little is known about the role of orexin signaling in motivation for opioids. Previously our lab showed that systemic blockade of orexin-1 receptors (Ox1Rs) decreases motivation for the potent and short-acting opioid remifentanil (Porter-Stransky et al., 2015). Previous studies also found that VP is an important site for the reinforcing effect of opiates and cocaine self-administration, as well as for reinstatement of drug seeking (Hubner and Koob, 1990; Mahler et al., 2014). However, it is unclear if orexin signaling in VP contributes to remifentanil demand. This study sought to determine whether intra-VP orexin signaling contributes to remifentanil demand and cue-induced reinstatement. We used a within-session behavioral economic (BE) paradigm in which remifentanil price (responses/μg iv remifentanil) was sequentially increased throughout the session. Rats were implanted with bilateral cannulae into VP, through which microinjections of SB334867 (SB; Ox1R antagonist) were given prior to BE testing. Rats were then extinguished and subjected to cue-induced reinstatement following intra-VP SB microinjection. We found that inhibition of OxR1 signaling in VP reduced motivation (increased demand elasticity) for remifentanil without affecting baseline consumption, cue induced reinstatement or general locomotor activity. These effects were not observed with aCSF injections into VP or SB injections 2 mm dorsal to VP (controls). These behavioral results provide evidence for orexin signaling in VP in motivation for the opioid remifentanil.
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