Nicotine-induced dopamine release in the nucleus accumbens is inhibited by the novel AMPA antagonist ZK200775 and the NMDA antagonist CGP39551

Abstract

Both NMDA- and AMPA receptors are involved in nicotine's dependence-producing properties, although in a spatiotemporally differential manner.

The Metabotropic Glutamate 2/3 Receptor Agonist LY379268 Blocked Nicotine-Induced Increases in Nucleus Accumbens Shell Dopamine only in the Presence of a Nicotine-Associated Context in Rats

“…The NAcc dopamine response (Experiment 1) after subcutaneous nicotine administration (0.4 mg/kg) in nicotine-naïve animals was similar to that reported previously (Bednar et al, 2004;Kosowski et al, 2004;Schilstrom et al, 1998). Similarly, increases in NAcc shell dopamine after subcutaneous nicotine administration (0.4 mg/kg) in nicotine-experienced animals (Experiment 2) were also consistent with previously published findings (Bednar et al, 2004;Benwell and Balfour, 1992;Cadoni and Di Chiara, 2000).…”

“…Nicotine increases glutamatergic transmission by activating excitatory nicotinic receptors located on presynaptic glutamatergic terminals (Fu et al, 2000;Mansvelder and McGehee, 2002;Reid et al, 2000). Blockade of glutamatergic neurotransmission by systemic administration of receptor antagonists that act at postsynaptically located ionotropic or metabotropic glutamate (mGlu) receptors attenuated both nicotine selfadministration (Kenny et al, 2009(Kenny et al, , 2003Palmatier et al, 2008;Paterson and Markou, 2005;Paterson et al, 2003) and nicotine-induced increases in NAcc dopamine release (Fu et al, 2000;Kosowski et al, 2004;Schilstrom et al, 1998;Sziraki et al, 2002).…”

NMDA Receptors Regulate Nicotine-Enhanced Brain Reward Function and Intravenous Nicotine Self-Administration: Role of the Ventral Tegmental Area and Central Nucleus of the Amygdala

“…These data suggest that AMPA receptors are not involved in nicotine reward, an observation consistent with the previous observations that systemic, intra-VTA, or intra-NAcc administration of the closely related AMPA receptor antagonist CNQX did not alter nicotine-induced increases in mesoaccumbens dopamine transmission (Schilstrom et al, 1998;Fu et al, 2000;Sziraki et al, 2002). However, a recent study demonstrated that ZK200775, an AMPA antagonist structurally related to NBQX and CNQX, attenuated nicotineinduced increases in NAcc dopamine release (Kosowski et al, 2004), suggesting a potential role for AMPA receptors in regulating nicotine reinforcement. One explanation for this apparent discrepancy is that ZK200775 may block populations of AMPA receptors distinct from those antagonized by NBQX (Kosowski et al, 2004).…”

“…However, a recent study demonstrated that ZK200775, an AMPA antagonist structurally related to NBQX and CNQX, attenuated nicotineinduced increases in NAcc dopamine release (Kosowski et al, 2004), suggesting a potential role for AMPA receptors in regulating nicotine reinforcement. One explanation for this apparent discrepancy is that ZK200775 may block populations of AMPA receptors distinct from those antagonized by NBQX (Kosowski et al, 2004). Alternatively, ZK200775 is less selective than NBQX for AMPA receptors compared with NMDA receptors (Randle et al, 1992;Kosowski et al, 2004), raising the possibility that the inhibitory actions of ZK200775 on nicotine-evoked NAcc dopamine release may reflect an indirect action at NMDA receptors.…”

“…One explanation for this apparent discrepancy is that ZK200775 may block populations of AMPA receptors distinct from those antagonized by NBQX (Kosowski et al, 2004). Alternatively, ZK200775 is less selective than NBQX for AMPA receptors compared with NMDA receptors (Randle et al, 1992;Kosowski et al, 2004), raising the possibility that the inhibitory actions of ZK200775 on nicotine-evoked NAcc dopamine release may reflect an indirect action at NMDA receptors. It is important to note that the doses of NBQX tested on nicotine self-administration behavior do not induce nonspecific decreases in operant performance (Jackson et al, 1996), but have been shown to precipitate withdrawal in nicotine-dependent rats (Kenny et al, 2003) and decrease responding for ethanol reinforcement (Stephens and Brown, 1999).…”