TY - JOUR
T1 - Involvement of the orexin/hypocretin system in ethanol conditioned place preference
AU - Voorhees, Charlene M.
AU - Cunningham, Christopher L.
N1 - Funding Information:
Acknowledgments This research was supported by NIH-NIAAA grants AA007702 and AA007468, ARCS Foundation, and an N.L. Tartar Research Fellowship. We would like to thank Dr. Tara Fidler and Peter Groblewski for their help in conducting Experiment 3 and the Portland Alcohol Research Center Core for assistance with BEC analysis. Experiments 1 and 4 were described in a published abstract and were presented at the Research Society on Alcoholism Annual Meeting in 2009. Portions of these data were also included in a thesis submitted in partial fulfillment of requirements for the Masters of Science Degree at the Oregon Health and Science University.
PY - 2011/4
Y1 - 2011/4
N2 - Rationale: Recent studies suggest that orexin/hypocretin is involved in drug reward and drug-seeking behaviors, including ethanol self-administration. However, orexin's role in ethanol-induced seeking behaviors remains unclear. Objective: These studies examined the role of orexin in the acquisition and expression of ethanol conditioned place preference (CPP) using the orexin 1 receptor (OX1R) antagonist SB-334867. Methods: Effects of SB-334867 (0-30 mg/kg) on locomotor activity were determined in DBA/2J mice (Experiment 1). SB-334867 (0-30 mg/kg) was administered during acquisition of ethanol (2 g/kg) CPP to determine whether orexin signaling is required (Experiment 2). Blood ethanol concentrations (BECs) were measured after ethanol (2 g/kg) injection to determine whether SB-334867 (30 mg/kg) pretreatment altered ethanol pharmacokinetics (Experiment 3). Finally, SB-334867 (0-40 mg/kg) was given before ethanol-free preference testing (Experiments 4 and 5). Results: SB-334867 did not alter basal locomotor activity (Experiment 1). SB-334867 (30 mg/kg) reduced ethanol-induced locomotor stimulation, but did not affect the acquisition of ethanol CPP (Experiment 2) or BEC, suggesting no alteration in ethanol pharmacokinetics (Experiment 3). Although OX1R antagonism blocked expression of a weak ethanol CPP (Experiment 4), it did not affect expression of a moderate to strong CPP (Experiment 5). Conclusions: Blockade of OX1R by systemic administration of SB-334867 reduced ethanol-stimulated activity, but did not affect acquisition or expression of ethanol-induced CPP, suggesting that orexin does not influence ethanol's primary or conditioned rewarding effects. Other neurotransmitter systems may be sufficient to support acquisition and expression of CPP despite alterations in orexin signaling.
AB - Rationale: Recent studies suggest that orexin/hypocretin is involved in drug reward and drug-seeking behaviors, including ethanol self-administration. However, orexin's role in ethanol-induced seeking behaviors remains unclear. Objective: These studies examined the role of orexin in the acquisition and expression of ethanol conditioned place preference (CPP) using the orexin 1 receptor (OX1R) antagonist SB-334867. Methods: Effects of SB-334867 (0-30 mg/kg) on locomotor activity were determined in DBA/2J mice (Experiment 1). SB-334867 (0-30 mg/kg) was administered during acquisition of ethanol (2 g/kg) CPP to determine whether orexin signaling is required (Experiment 2). Blood ethanol concentrations (BECs) were measured after ethanol (2 g/kg) injection to determine whether SB-334867 (30 mg/kg) pretreatment altered ethanol pharmacokinetics (Experiment 3). Finally, SB-334867 (0-40 mg/kg) was given before ethanol-free preference testing (Experiments 4 and 5). Results: SB-334867 did not alter basal locomotor activity (Experiment 1). SB-334867 (30 mg/kg) reduced ethanol-induced locomotor stimulation, but did not affect the acquisition of ethanol CPP (Experiment 2) or BEC, suggesting no alteration in ethanol pharmacokinetics (Experiment 3). Although OX1R antagonism blocked expression of a weak ethanol CPP (Experiment 4), it did not affect expression of a moderate to strong CPP (Experiment 5). Conclusions: Blockade of OX1R by systemic administration of SB-334867 reduced ethanol-stimulated activity, but did not affect acquisition or expression of ethanol-induced CPP, suggesting that orexin does not influence ethanol's primary or conditioned rewarding effects. Other neurotransmitter systems may be sufficient to support acquisition and expression of CPP despite alterations in orexin signaling.
KW - Conditioned place preference
KW - Inbred mice (DBA/2J)
KW - Locomotor activity
KW - Orexin
KW - SB-334867
UR - http://www.scopus.com/inward/record.url?scp=79953650672&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953650672&partnerID=8YFLogxK
U2 - 10.1007/s00213-010-2082-6
DO - 10.1007/s00213-010-2082-6
M3 - Article
C2 - 21107540
AN - SCOPUS:79953650672
SN - 0033-3158
VL - 214
SP - 805
EP - 818
JO - Psychopharmacology
JF - Psychopharmacology
IS - 4
ER -