Stimuli linked to ethanol availability activate hypothalamic CART and orexin neurons in a reinstatement model of relapse.
BACKGROUND
There has been a recent upsurge of interest in the role of hypothalamic feeding peptides, in particular, orexin (hypocretin), in drug-seeking behavior. However, the potential role of other hypothalamic feeding peptides, such as cocaine- and amphetamine-regulated transcript (CART), in conditioned reinstatement has yet to be explored.


METHODS
Animals were exposed to environmental stimuli previously associated with ethanol availability (EtOH S+), and sections from the hypothalamus and paraventricular thalamus (PVT), a recipient of CART and orexin innervation, were dual labeled for Fos-protein and either CART or orexin.


RESULTS
Significantly larger numbers of Fos-positive arcuate nucleus CART and hypothalamic orexin neurons were seen in animals exposed to the EtOH S+ compared with nonreward S- animals. Presentation of the EtOH S+ also increased numbers of Fos-positive PVT neurons. Fos-positive PVT neurons were observed to be closely associated with orexin and CART terminal fields.


CONCLUSIONS
Taken together, these findings suggest that activation of hypothalamic neuropeptide systems may be a common mechanism underlying drug-seeking behavior.
Dayas
Christopher V
CV
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA, USA. Christopher.Dayas@newcastle.edu.au
McGranahan
Tresa M
TM
Martin-Fardon
Rémi
R
Weiss
Friedbert
F
D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D007031:Hypothalamus / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D002492:Central Nervous System Depressants; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000068797:Orexins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000431:Ethanol