Orexin-mediated restoration of hippocampal synaptic potentiation in mice with established cocaine-conditioned place preference
Journal
Addiction biology
Journal Volume
24
Journal Issue
6
Pages
1153
Date Issued
2019-11
Author(s)
Abstract
Orexins (also called hypocretins) are implicated in reward and addiction, but little is known about their role(s) in the association between hippocampal synaptic plasticity and drug preference. Previously, we found that exogenous orexin via OX1 and OX2 receptors can impair low frequency stimulation-induced depotentiation, i.e. restoring potentiation of excitatory synaptic transmission (re-potentiation) in mouse hippocampal slices. Here, we found this re-potentiation in hippocampal slices from mice that had acquired conditioned place preference (CPP) to cocaine. Both 10 and 20 mg/kg of cocaine induced similar magnitudes of CPP in mice and re-potentiation in their hippocampal slices, but differed in their susceptibility to TCS1102, a dual (OX1 and OX2 ) orexin receptor antagonist. TCS1102 significantly attenuated CPP and hippocampal re-potentiation induced by cocaine at 10 mg/kg but not at 20 mg/kg. Nonetheless, SCH23390, an antagonist of dopamine D1-like receptors (D1-likeRs), inhibited the effects induced by both doses of cocaine. SKF38393, a D1-likeR-selective agonist, also induced hippocampal re-potentiation in vitro. Interestingly, this effect was attenuated by TCS1102. Conversely, SCH23390 prevented orexin A-induced hippocampal re-potentiation. These results suggest that endogenous orexins are released in mice during cocaine-CPP acquisition, which sustains potentiated hippocampal transmission via OX1 /OX2 receptors and may contribute to the addiction memory of cocaine. This effect of endogenous orexins, however, may be substituted by dopamine that may dominate hippocampal re-potentiation and CPP via D1-likeRs when the reinforcing effect of cocaine is high.
Subjects
cocaine-induced conditioned place preference; hippocampal synaptic plasticity; orexin
SDGs
Publisher
WILEY
Type
journal article