Metabotropic glutamate 2/3 receptor activation induced reward deficits but did not aggravate brain reward deficits associated with spontaneous nicotine withdrawal in rats.
Glutamate neurotransmission, and particularly metabotropic glutamate (mGlu) 2/3 receptors are implicated in behaviors of relevance to the addictive properties of nicotine. In laboratory animals, the mGlu2/3 receptor agonist LY379268 has been previously shown to decrease intravenous nicotine self-administration and cue-induced reinstatement of nicotine-seeking behavior. Such mGlu2/3 receptor agonists may therefore be useful medications to assist people in smoking cessation. Because of the demonstrated preclinical efficacy of mGlu2/3 receptor agonists in decreasing the primary rewarding and conditioned effects of nicotine in rats, we wished to examine whether such compounds could potentially influence additional aspects of nicotine dependence, such as nicotine withdrawal. We hypothesized that an mGlu2/3 receptor agonist would have negative effects on nicotine withdrawal because mGlu2/3 receptor antagonists have previously been shown to attenuate nicotine withdrawal-induced reward deficits, while an mGlu2/3 receptor agonist precipitated withdrawal-like reward deficits in rats dependent on nicotine. To test this hypothesis, we assessed the effects of the mGlu2/3 receptor agonist LY379268 on brain reward deficits associated with spontaneous nicotine withdrawal in rats. Brain reward function, as assessed by intracranial self-stimulation reward thresholds, was examined after removal of nicotine- or saline-delivering subcutaneous osmotic minipumps. LY379268 administration produced reward deficits in animals "withdrawing" from chronic saline administration and only tended to aggravate nicotine withdrawal-induced reward deficits in rats previously treated with nicotine. Thus, this mGlu2/3 agonist does not appear to significantly influence the affective depression-like aspects of nicotine withdrawal.
Liechti
Matthias E
ME
Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Markou
Athina
A
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D009538:Nicotine