共 29 条
Intermittent ethanol consumption depresses endocannabinoid-signaling in the dorsolateral striatum of rat
被引:50
作者:
Adermark, Louise
[1
]
Jonsson, Susanne
[1
]
Ericson, Mia
[1
]
Soderpalm, Bo
[1
]
机构:
[1] Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Addict Biol Unit, S-40530 Gothenburg, Sweden
基金:
英国医学研究理事会;
关键词:
Alcohol;
Basal ganglia;
Cannabinoid;
1;
receptor;
GABA;
Long-term;
Synaptic plasticity;
LONG-TERM DEPRESSION;
DEPENDENT PLASTICITY;
SYNAPTIC PLASTICITY;
NUCLEUS-ACCUMBENS;
DORSAL STRIATUM;
WISTAR RATS;
DOPAMINE;
STRESS;
REWARD;
RECEPTORS;
D O I:
10.1016/j.neuropharm.2011.01.014
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
Recent research suggests that 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. In this study, endocannabinoid (eCB) signaling in the dorsolateral striatum, a brain region vital for habit formation, was evaluated in acutely isolated brain slices from ethanol (EtOH)-consuming rats and control rats. EtOH-consuming rats had free access to a 20% EtOH solution for three 24 hour sessions a week during seven weeks and consumed an average of 3.4 g/kg per session. eCB-mediated long-lasting disinhibition (DLL) of population spike (PS) amplitude induced by moderate frequency stimulation was impaired in EtOH-consuming rats, and was not restored by the muscarinic receptor antagonist scopolamine (10 mu M). The lack of DLL could be linked to a reduced GABA(A) receptor tone, since bicuculline-mediated disinhibition of striatal output was significantly reduced in slices from EtOH-consuming rats. However, eCB signaling induced by high frequency stimulation (HFS) was also impaired in slices from EtOH-consuming rats and isolated control rats. Activation of presynaptic cannabinoid 1 receptors (CB1R) with WIN55,212-2 (250 nM, 1 mu M) significantly modulated PS amplitude in slices from age-matched control rats while slices from EtOH-consuming rats remained unaffected, indicating that eCB signaling is inhibited at a level that is downstream from CB1R activation. Intermittent alcohol intake for seven weeks might thus be sufficient to modulate a presynaptic mechanism that needs to be synergized with CB1R activation for induction of long-term depression (LTD). In conclusion, alcohol consumption inhibits striatal eCB signaling in a way that could be of importance for understanding the neurological underpinnings of addictive behavior. This article is part of a Special Issue entitled 'Synaptic Plasticity and Addiction'. (C) 2011 Elsevier Ltd. All rights reserved.
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页码:1160 / 1165
页数:6
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