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

• 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 50mM EtOH but not 20, 80 or 100mM, 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, 50μM), but is blocked in slices treated with glycine receptor antagonists (strychnine, 1μM; PMBA, 50μM), nicotinic acetylcholine receptor antagonists (mecamylamine, 10μM; methyllycaconitine citrate (MLA), 40nM), or GABA(A) receptor inhibitors (picrotoxin, 100μM; bicuculline, 2μM, 20μM). A long-term facilitation of synaptic output, which is more pronounced in slices from adult Wistar rats, is detected following EtOH washout (50, 80, 100mM). 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 (10μM). Administration of 100mM 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

Nyckelord

Animals

Corpus Striatum

drug effects

physiology

Ethanol

pharmacology

Female

Interneurons

physiology

Male

Rats

Rats

Wistar

Receptors

Cholinergic

metabolism

Synapses

drug effects

metabolism

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