TY - JOUR
T1 - The oxytocin receptor impairs ethanol reward in mice
AU - Bahi, Amine
N1 - Funding Information:
This work was supported by grants from the United Arab Emirates University (Grant No. NP/13/05 ) and the National Research Foundation (Grant No. 31M082 ). The funders had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Publisher Copyright:
© 2013 Elsevier Inc.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - It is well established that oxytocin, and its receptor (OxtR), play a crucial role in addiction and that the stimulation of oxytocin neurotransmission reduces addictive behaviors to ethanol in laboratory animals. However, the impact of OxtR modulation on acquisition, extinction and reinstatement of drug-elicited ethanol-conditioned place preference (EtOH-CPP) has not yet been investigated. In this study, we evaluated the effects of OxtR pharmacological modulation, using the oxytocin analog Carbetocin, and genetic overexpression in the nucleus accumbens (NAcc), using lentiviral-mediated gene transfer technology, of the OxtR on acquisition, extinction and reinstatement of drug-elicited EtOH-CPP in mice. In the first experiment, results showed that Carbetocin administration and NAcc OxtR-overexpression (LV-OxtR) reduced EtOH-CPP establishment. In the second experiment, systemic Carbetocin treatment and OxtR overexpression resulted in decreased time spent in the ethanol-paired compartment following completion of a 7-day extinction protocol. Finally, the third experiment showed that Carbetocin and LV-OxtR suppressed primed reinstatement of EtOH-CPP. It is concluded that pharmacological and genetic modulation of the OxtR can modulate the acquisition, extinction, and reinstatement of conditioned reinforcing effects of ethanol. Taken together, the current findings add to the growing literature on oxytocin neurotransmission modulation in the pharmacotherapy of ethanol addiction and alcoholism.
AB - It is well established that oxytocin, and its receptor (OxtR), play a crucial role in addiction and that the stimulation of oxytocin neurotransmission reduces addictive behaviors to ethanol in laboratory animals. However, the impact of OxtR modulation on acquisition, extinction and reinstatement of drug-elicited ethanol-conditioned place preference (EtOH-CPP) has not yet been investigated. In this study, we evaluated the effects of OxtR pharmacological modulation, using the oxytocin analog Carbetocin, and genetic overexpression in the nucleus accumbens (NAcc), using lentiviral-mediated gene transfer technology, of the OxtR on acquisition, extinction and reinstatement of drug-elicited EtOH-CPP in mice. In the first experiment, results showed that Carbetocin administration and NAcc OxtR-overexpression (LV-OxtR) reduced EtOH-CPP establishment. In the second experiment, systemic Carbetocin treatment and OxtR overexpression resulted in decreased time spent in the ethanol-paired compartment following completion of a 7-day extinction protocol. Finally, the third experiment showed that Carbetocin and LV-OxtR suppressed primed reinstatement of EtOH-CPP. It is concluded that pharmacological and genetic modulation of the OxtR can modulate the acquisition, extinction, and reinstatement of conditioned reinforcing effects of ethanol. Taken together, the current findings add to the growing literature on oxytocin neurotransmission modulation in the pharmacotherapy of ethanol addiction and alcoholism.
KW - Acquisition
KW - CPP
KW - Carbetocin
KW - Extinction
KW - Oxytocin
KW - Reinstatement
KW - Viral vectors
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U2 - 10.1016/j.physbeh.2014.11.046
DO - 10.1016/j.physbeh.2014.11.046
M3 - Article
C2 - 25449413
AN - SCOPUS:84912129976
SN - 0031-9384
VL - 139
SP - 321
EP - 327
JO - Physiology and Behavior
JF - Physiology and Behavior
ER -