Some of the pivotal components of the neurocircuitry of addiction ( Koob and Volkow, 2010) receive projections from the PVT ( Kirouac, 2015), highlighting the potential importance of this thalamic nucleus in the regulation of compulsive drug seeking that characterizes addiction. The PVT is selectively recruited during cocaine-seeking behavior that is induced by the presentation of cocaine-predictive stimuli ( Matzeu et al., 2017), and its integrity is necessary for behavior that is motivated by the presentation of cocaine-predictive environmental stimuli ( Matzeu et al., 2015). The PVT has attracted interest because of its connections with limbic and cortical structures that are part of the neurocircuitry that mediates drug-seeking behavior ( Everitt et al., 2001 McFarland and Kalivas, 2001 Ito et al., 2002 Kalivas and Volkow, 2005 Belin and Everitt, 2008 Steketee and Kalivas, 2011). The PVT has been consistently shown to be activated during periods of arousal and stressful conditions ( Peng et al., 1995 Bhatnagar and Dallman, 1998 Novak and Nunez, 1998 Bubser and Deutch, 1999 Novak et al., 2000 Otake et al., 2002). The paraventricular nucleus of the thalamus (PVT) plays a major role in regulating arousal, attention, awareness states, food consumption, and energy balance ( Bentivoglio et al., 1991 Groenewegen and Berendse, 1994 Van der Werf et al., 2002 Colavito et al., 2015 Kirouac, 2015). Furthermore, these findings suggest that throughout abstinence, the Orx↔pPVT connection undergoes neuroadaptive changes, reflected by alterations of the number of OrxR2-expressing cells in the pPVT. These data build on our previous findings that the hypothalamic Orx↔pPVT connection is strongly recruited shortly after cocaine abstinence and demonstrate that the priming effect of OrxA is not long lasting. In the pPVT, the number of OrxR2-expressing cells was significantly higher only at intermediate abstinence, with no changes in the number of OrxR1-expressing cells. A higher number of cells that expressed Orx was observed in the LH/DMH/PFA at both intermediate and protracted abstinence. At protracted abstinence, however, the priming effect of OrxA was absent. Orexin A administration in the pPVT induced cocaine-seeking behavior after intermediate abstinence, as reported previously. Furthermore, to better understand whether a history of cocaine dependence affects the Orx system-particularly the hypothalamic Orx↔pPVT connection-the number of Orx-expressing cells in the lateral hypothalamus (LH), dorsomedial hypothalamus (DMH), and perifornical area (PFA) and number of orexin receptor 1 (OrxR1)- and OrxR2-expressing cells in the pPVT were quantified. Considering the long-lasting nature of drug-seeking behavior, the present study examined whether the priming effect of intra-pPVT OrxA administration was preserved after a period of protracted abstinence (4–5 weeks) in rats that self-administered cocaine under LgA conditions. Using an established model of cocaine dependence (i.e., long access to cocaine), we previously showed that OrxA injections in the posterior PVT (pPVT) reinstated extinguished cocaine-seeking behavior in rats after an intermediate period of abstinence (2–3 weeks). Hypothalamic orexin (Orx) projections to the paraventricular nucleus of the thalamus (PVT) have received growing interest because of their role in drug-seeking behavior.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |