Details

Autor(en) / Beteiligte

• Adermark, Louise
• Clarke, Rhona B.C.
• Söderpalm, Bo
• Ericson, Mia

Titel

Ethanol-induced modulation of synaptic output from the dorsolateral striatum in rat is regulated by cholinergic interneurons

Ist Teil von

• Neurochemistry international, 2011-05, Vol.58 (6), p.693-699

Ort / Verlag

Kidlington: Elsevier Ltd

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• ► Ethanol exerts dual actions on striatal output that are initiated simultaneously. ► Acute ethanol-treatment induces a GABAAR-sensitive short-term depression. ► Ethanol washout induces a long-term facilitation of striatal output. ► Ethanol-induced facilitation is regulated by cholinergic interneurons. ► This study provide important clues for understanding acute ethanol intoxication. The striatum is the largest input nucleus to the basal ganglia and associated with reward-based behavior. We assessed whether acute ethanol (EtOH) exposure could modulate synaptic efficacy in the dorsolateral striatum of juvenile Wistar rats. Since acute EtOH administration can both increase and decrease the probability of release of different neurotransmitters from synaptic terminals, we used field potential recordings to evaluate the net effect of EtOH on striatal output. We showed that 50 mM EtOH but not 20, 80 or 100 mM, depresses population spike (PS) amplitude in the dorsolateral striatum. This depression of synaptic output is insensitive to the N-methyl- d-aspartic acid (NMDA) receptor inhibitor DL-2-amino-5-phosphonopentanoic acid (AP-5, 50 μM), but is blocked in slices treated with glycine receptor antagonists (strychnine, 1 μM; PMBA, 50 μM), nicotinic acetylcholine receptor antagonists (mecamylamine, 10 μM; methyllycaconitine citrate (MLA), 40 nM), or GABA A receptor inhibitors (picrotoxin, 100 μM; bicuculline, 2 μM, 20 μM). A long-term facilitation of synaptic output, which is more pronounced in slices from adult Wistar rats, is detected following EtOH washout (50, 80, 100 mM). This long-term enhancement of PS amplitude is regulated by cholinergic interneurons and completely blocked by mecamylamine, MLA or the non-selective muscarinic antagonist scopolamine (10 μM). Administration of 100 mM EtOH significantly depresses PS amplitude in scopolamine-treated slices, suggesting that EtOH exerts dual actions on striatal output that are initiated instantly upon drug wash-on. In conclusion, EtOH modulates striatal microcircuitry and neurotransmission in a way that could be of importance for understanding the intoxicating properties as well as the acute reward sensation of EtOH.