Neurokinin type-3 receptor stimulation impairs ethanol-associated appetitive behavior in Wistar rats.
OBJECTIVE
Stimulating central neurokinin type-3 (NK-3) receptors decreases ethanol intake in rats. Although paraventricular nucleus of the hypothalamus (PVN) has a high density of NK-3 receptors, their influence on ethanol reinforcement has not been examined. This study's purpose was to assess the effects of intra-PVN infusion of senktide, a NK-3 receptor agonist, on ethanol self-administration. In a follow-up study, senktide's effects on ethanol self-administration after intracerebroventricular (ICV) infusion were examined.


METHODS
Male Wistar rats were trained to self-administer 10% ethanol (10E) in the "Sipper Tube" model described by Samson and colleagues, Guide cannula were then aimed bilaterally at the PVN or unilaterally at the lateral cerebral ventricle. Intra-PVN (5-100 ng/side) or ICV (30-500 ng/rat) effects of senktide on 10E self-administration were also examined as a preliminary test of senktide's selectivity.


RESULTS
Intra-PVN and ICV infusion of senktide reduced the average number of consecutive lever presses and increased the time taken to complete the lever press requirement when 10E served as the reinforcer. Increased duration of the lever-pressing component was observed when senktide was administered prior to 2S self-administration sessions. Neither PVN nor ICV senktide administration significantly altered 10E or 2S consumption.


CONCLUSIONS
These data suggest that stimulation of central neurokinin typ-3 receptors in the Wistar rat reduces appetitive behavior while having little or no impact on consummatory behavior. Ethanol "seeking" appeared more sensitive to disruption by senktide than sucrose "seeking." However, further studies assessing the senktide's effects on sucrose-maintained behavior are needed to verify this hypothesis. Lastly, it is hypothesized that lack of effect of senktide on intake is in part related to the use of outbred Wistar rats in these studies instead of selectively bred rats.
Slawecki
Craig J
CJ
The Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037, USA. cslawecki@scripps.edu
Roth
Jennifer
J
D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000378:metabolism* / Q000502:physiology; D012646:Self Administration; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives*
D010446:Peptide Fragments; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; D000431:Ethanol