Behavioral changes after nicotine challenge are associated with α7 nicotinic acetylcholine receptor-stimulated glutamate release in the rat dorsal striatum

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.

Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

“…The present study indicated that co-exposure of EtOH and NIC increased mGlurR1 expression in the NAc. Studies have found that phasic exposure to EtOH or NIC resulted in a marked increase in the total extracellular concentrations of glutamate, which might indicate increased firing of medium spiny neurons (Griffin III et al, 2014, Griffin et al, 2015, Ryu et al, 2017. We suggest here that this A C C E P T E D M A N U S C R I P T 20 effect might increase the expression of post-synaptic glutamate receptors such as mGluR1 as a compensatory mechanism.…”

Does kynurenic acid act on nicotinic receptors? An assessment of the evidence

“…The two major subtypes of CNS nicotinic receptors, α7 and α4β2 are expressed on cell bodies and synaptic terminals (Wonnacot, ; Parikh et al , ; Puddifoot et al ; Howe et al ) where they promote the influx of extracellular calcium leading to the release of neurotransmitters (Turner ; Zappettini et al , ). Nicotinic receptors can regulate the release of, at least, glutamate (McGehee et al, ; Gray et al, ; Albuquerque et al ; Gu et al, ; Puddifoot et al ; Pistillo et al , ; Howe et al ; Ryu et al ) and can modulate the release of GABA (Gray et al, ; Le Magueresse et al, ), dopamine (Schilstrom et al, ,b; Kaiser and Wonnacott ; Livingstone and Wonnacott, ; Livingstone et al ) and norepinephrine (Pittaluga and Raiteri ; Pittaluga et al ; Raiteri et al ; Li et al, ). It is reasonable to expect that the release of many other transmitters and modulators including serotonin, glycine, neuroactive peptides and perhaps kynurenines, proteases, cytokines and other factors may also be affected by nicotinic receptors on glia or synaptic terminals or cell bodies.…”

Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization

“…The dose used for subcutaneous (s.c.) nicotine (0.4 mg/kg/day) administration was determined from previous studies (Matta et al, 2007 ; Ryu et al, 2017 ). The extracted CSC was dissolved in 1% DMSO/0.9% NaCl and diluted to make working solutions with a nicotine content of 0.4 mg, and were then adjusted to pH 7.2–7.4 with NaOH.…”

“…For example, repeated exposure to nicotine increases glutamate release in the NAc, VTA and PFC by stimulating nAChRs (Lambe et al, 2003 ; Changeux, 2010 ; Shameem and Patel, 2012 ; Falasca et al, 2014 ). Repeated and challenge administrations of nicotine after nicotine abstinence following repeated nicotine exposure also potentiate glutamate levels in the dorsal striatum (Ryu et al, 2017 ). These findings suggest hyperactivation of the cholinergic system in mesolimbic and nigrostriatal projection neurons after nicotine exposure triggers the upregulation of glutamatergic neurotransmission.…”

“…This behavioral sensitization is mediated by signaling cascades linked to ionotropic and metabotropic glutamate receptors in the dorsal striatum, NAc and PFC (Kozell and Meshul, 2001 ; Kalivas, 2004 ; Kalivas et al, 2009 ; Lu et al, 2014 ; Liu and Steketee, 2016 ). Repeated or challenge exposure to nicotine increases psychomotor activity, including locomotor and rearing activities, by activating glutamatergic response in the dorsal striatum (Ryu et al, 2017 ). Together, these findings suggest that enhancement of glutamatergic neurotransmission in the dorsal striatum by nicotine exposure is closely associated with psychomotor sensitization caused by the psychoactive properties of nicotine.…”