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Phenotype‐dependent inhibition of glutamatergic transmission on nucleus accumbens medium spiny neurons by the abused inhalant toluene
Author(s) -
Beckley Jacob T.,
Randall Patrick K.,
Smith Rachel J.,
Hughes Benjamin A.,
Kalivas Peter W.,
Woodward John J.
Publication year - 2016
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12235
Subject(s) - medium spiny neuron , nucleus accumbens , ampa receptor , neuroscience , glutamatergic , neurotransmission , nmda receptor , chemistry , excitatory postsynaptic potential , conditioned place preference , pharmacology , glutamate receptor , dopamine , biology , inhibitory postsynaptic potential , receptor , biochemistry , striatum
Abused inhalants are voluntarily inhaled at high concentrations to produce intoxicating effects. Results from animal studies show that the abused inhalant toluene triggers behaviors, such as self‐administration and conditioned place preference, which are commonly associated with addictive drugs. However, little is known about how toluene affects neurons within the nucleus accumbens ( NAc ), a brain region within the basal ganglia that mediates goal‐directed behaviors and is implicated in the development and maintenance of addictive behaviors. Here we report that toluene inhibits a component of the after‐hyperpolarization potential, and dose‐dependently inhibits N ‐methyl‐ D ‐aspartate (NMDA)‐mediated currents in rat NAc medium spiny neurons ( MSN ). Moreover, using the multivariate statistical technique, partial least squares discriminative analysis to analyze electrophysiological measures from rat NAc MSNs , we show that toluene induces a persistent depression of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐mediated currents in one subtype of NAc MSN s, and that the electrophysiological features of MSN neurons predicts their sensitivity to toluene. The CB 1 receptor antagonist AM 281 blocked the toluene‐induced long‐term depression of AMPA currents, indicating that this process is dependent on endocannabinoid signaling. The neuronal identity of recorded cells was examined using dual histochemistry and shows that toluene‐sensitive NAc neurons are dopamine D 2 MSNs that express preproenkephalin mRNA . Overall, the results from these studies indicate that physiological characteristics obtained from NAc MSNs during whole‐cell patch‐clamp recordings reliably predict neuronal phenotype, and that the abused inhalant toluene differentially depresses excitatory neurotransmission in NAc neuronal subtypes.