Acute ethanol treatment prevents endocannabinoid-mediated long-lasting disinhibition of striatal output.
Recent research has suggested that the neuronal circuit adaptations elicited by drugs of abuse share common features with traditional learning models, and that drugs of abuse cause long-term changes in behavior by altering synaptic function and plasticity. Especially, the endocannabinoid (eCB) system appears to be involved in the neuronal circuitry regulating ethanol (EtOH) preference in rodent. The aim of this study was to evaluate if acute EtOH exposure could modulate eCB-mediated plasticity in the dorsolateral striatum. Our data show that EtOH (20-50 mM) prevents eCB-mediated long-lasting disinhibition (DLL) of striatal output induced by a single stimulation train delivered at 5 Hz for 60 s, and reduces long-term depression (LTD) induced by low-frequency stimulation at inhibitory synapses. Acute EtOH-treatment also prevents DLL induced by the L-type calcium channel activator 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methylester (FPL64176; 500 nM), or by the cannabinoid 1 receptor (CB(1)R) agonist WIN55,212-2 (300 nM), indicating that EtOH affects eCB-signaling at a stage that is downstream from eCB production and release. Importantly, high-frequency stimulation, or a higher concentration of WIN55,212-2 (1 muM), induces EtOH-insensitive depression of striatal output, suggesting that EtOH affects CB(1)R-mediated signaling in a synapse-specific manner. Maintaining the balance between excitation and inhibition is vital for neuronal networks, and EtOH-mediated modulation of eCB-signaling might thus affect the stability and the fine-tuning of neuronal circuits in the striatum. Our data suggest that changes in eCB-signaling could be involved in the physiological response to acute alcohol intoxication.
Clarke
Rhona B C
RB
Addiction Biology Unit, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Box 410, 405 30 Gothenburg, Sweden.
Adermark
Louise
L
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D063388:Endocannabinoids; D000431:Ethanol / Q000008:administration & dosage*; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D000431:Ethanol