Behavioral changes after nicotine challenge are associated with \u03b17 nicotinic acetylcholine receptor-stimulated glutamate release in the rat dorsal striatum

In Soo Ryu,In Soo Ryu,Su Yeon Seo,Ju Hwan Yang,Eun Sang Choe,Hyun-Wook Cho,Hee Young Kim,Joung-Wook Seo,Suchan Chang,Insop Shim,Seong Shoon Yoon,Jieun Kim,Jeong Hwan Oh,Dong Kun Lee

doi:10.1038/s41598-017-15161-7

Abstract

Neurochemical alterations associated with behavioral responses induced by re-exposure to nicotine have not been sufficiently characterized in the dorsal striatum. Herein, we report on changes in glutamate concentrations in the rat dorsal striatum associated with behavioral alterations after nicotine challenge. Nicotine challenge (0.4 mg/kg/day, subcutaneous) significantly increased extracellular glutamate concentrations up to the level observed with repeated nicotine administration. This increase occurred in parallel with an increase in behavioral changes in locomotor and rearing activities. In contrast, acute nicotine administration and nicotine withdrawal on days 1 and 6 did not alter glutamate levels or behavioral changes. Blockade of α7 nicotinic acetylcholine receptors (nAChRs) significantly decreased the nicotine challenge-induced increases in extracellular glutamate concentrations and locomotor and rearing activities. These findings suggest that behavioral changes in locomotor and rearing activities after re-exposure to nicotine are closely associated with hyperactivation of the glutamate response by stimulating α7 nAChRs in the rat dorsal striatum.

Highlights

Neurochemical alterations associated with behavioral responses induced by re-exposure to nicotine have not been sufficiently characterized in the dorsal striatum
The results demonstrated that treatment with the potent α7 nicotinic acetylcholine receptors (nAChRs) antagonist, methyllycaconitine citrate (MLA), prior to nicotine challenge administration significantly decreased the nicotine challenge-induced increases in output currents (Fig. 7b) and glutamate concentrations (Time, F(24,96) = 4.345, p < 0.0001; Treatment, F(1,4) = 38.88, p = 0.0034; Time × Treatment, F(24,96) = 8.345, p < 0.0001) (Fig. 7c) compared to those resulting from nicotine challenge administration followed by vehicle pretreatment
Long-term exposure to nicotine enhances its reinforcing property by stimulating the excitatory α7 nAChRs, which leads to a glutamate release in the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus[8,35,36]

Summary

Introduction

Neurochemical alterations associated with behavioral responses induced by re-exposure to nicotine have not been sufficiently characterized in the dorsal striatum. Blockade of α7 nicotinic acetylcholine receptors (nAChRs) significantly decreased the nicotine challenge-induced increases in extracellular glutamate concentrations and locomotor and rearing activities These findings suggest that behavioral changes in locomotor and rearing activities after re-exposure to nicotine are closely associated with hyperactivation of the glutamate response by stimulating α7 nAChRs in the rat dorsal striatum. Tobacco use, such as cigarette smoking, can cause dependence, which is a psychiatric disorder (DSM-V) characterized by compulsive drug intake and various withdrawal symptoms, such as anhedonia, dysphoria, anxiety, irritability, and craving[1,2,3,4,5]. We demonstrate a novel result, which shows that re-exposure to nicotine increases extracellular glutamate release by stimulating α7 nAChRs in the rat dorsal striatum, which may contribute to alter locomotor and rearing activities

Methods

Results

Conclusion