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Athina Markou: Influence Statistics

Stimulatory actions of nicotine on mesocorticolimbic dopamine transmission are partly mediated by nicotine-induced glutamate release acting on ionotropic and metabotropic glutamate (mGlu) receptors. Because both presynaptic inhibitory mGlu2/3 and postsynaptic excitatory mGlu5 receptors provide potential targets for treatment of aspects of nicotine dependence, we examined interacting effects of mGlu5 (2-methyl-6-(phenylethynyl)-pyridine, MPEP) and mGlu2/3 (LY341495) receptor antagonists ...

RationalePrevious work has indicated a potential role for γ-aminobutyric acid-B (GABAB) receptor agonists in treating drug addiction in humans. Specifically, GABAB receptor agonists decreased cocaine, heroin and nicotine self-administration in rats.ObjectivesThe purpose of the present studies was to extend previous findings by assessing the effects of additional GABAB receptor agonists on nicotine self-administration and food-maintained responding, under both fixed and progressive ratio ...

Acute administration of gamma-aminobutyric acid (GABA)-B receptor agonists decreases nicotine, cocaine, ethanol, and heroin self-administration and also decreases food-maintained responding and suppresses locomotor activity at high doses. GABA(B) receptor-positive modulators may represent potentially improved therapeutic compounds because of their fewer side effects than receptor agonists. The present study investigated the effects of administration of the GABA(B) receptor-positive ...

Previous studies suggested that metabotropic glutamate 5 (mGlu5) receptors play an important role in the reinforcing effects of abused drugs. The present experiments evaluated the effects of the mGlu5 receptor antagonist, MPEP (2-methyl-6-(phenylethynyl)-pyridine hydrochloride; 1-10 mg/kg, salt, i.p.), in rat models of nicotine-seeking behavior that may have relevance to relapse to drug-taking. Male Wistar rats (with restricted access to food) were trained to nose-poke to receive ...

RationaleThe aversive aspects of nicotine withdrawal contribute to high relapse rates to tobacco smoking after cessation attempts.ObjectivesTo investigate the influence of nicotine dose, duration of nicotine exposure, and withdrawal history on the severity of nicotine withdrawal in rats, as assessed by brain stimulation reward thresholds and somatic signs of withdrawal.MethodsRepeated spontaneous and precipitated withdrawals were investigated through four successive removals of osmotic ...

RationaleNicotine increases glutamate release in the ventral tegmental area and the nucleus accumbens, and thus enhances dopamine neurotransmission in the mesolimbic system that has been implicated in mediating the rewarding effects of drugs. Metabotropic glutamate receptors 5 (mGluR5) are found in the nucleus accumbens and may play a role in modulating the post-synaptic response to both glutamate and dopamine.ObjectivesThe present study investigated the effects of the mGluR5 antagonist ...

RationaleBupropion is an atypical antidepressant and the only non-nicotine-based therapy approved for smoking cessation. Its use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation.ObjectivesWe assessed the effects of bupropion on brain reward function under baseline conditions and subsequent to withdrawal from chronic nicotine administration in rats.MethodsA discrete-trial intracranial self-stimulation paradigm procedure was used that provides one ...

This study investigated the role of ionotropic and metabotropic glutamate receptors in the deficits in brain reward function, as measured by elevations in intracranial self-stimulation (ICSS) reward thresholds, associated with nicotine withdrawal. The group II metabotropic glutamate (mGluII) receptor agonist LY314582 [a racemic mixture of LY354740 ([+]-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid])] (2.5-7.5 mg/kg) precipitated withdrawal-like elevations in ICSS thresholds, a ...

Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5–2.5 mg per kg) abolished nicotine-enhanced brain ...

Acute administration of γ-aminobutyric acid B (GABAB) receptor agonists decreased nicotine, cocaine, ethanol, and heroin self-administration. GABAB receptor agonists also decreased cue-induced cocaine craving or seeking in humans and animals, respectively. The present study investigated the effects of repeated subcutaneous administration of the GABAB receptor agonist CGP44532 on nicotine- and food-maintained responding under a fixed ratio 5 schedule of reinforcement. The second part of ...

RationaleThe metabotropic glutamate (mGlu5) receptor subtype 5 antagonist MPEP attenuates self-administration of numerous drugs of abuse.ObjectivesThe purpose of the present study was to explore whether MPEP-induced decreases in nicotine and cocaine self-administration reflect attenuation of the reinforcing and incentive motivational effects of nicotine and cocaine. The effects of MPEP on breaking points maintained by nicotine, cocaine or food were assessed using a progressive ratio ...

Phencyclidine (PCP), a non-competitive antagonist of ionotropic N-methyl-D-aspartate (NMDA) receptors, produces psychotomimetic effects, such as a disruption in prepulse inhibition (PPI) of the startle response. NMDA antagonists also induce locomotor hyperactivity in rodents. We hypothesized that, like NMDA receptors, metabotropic glutamate receptors (mGluRs) modulate PPI and locomotor activity either alone or, in the case of mGluR5, via interaction with NMDA receptors. Rats treated with ...

In these experiments we sought to establish the intravenous (IV) self-administration of cocaine under a second-order schedule of reinforcement in order: (i) to obtain reliable, drug-free levels of responding with cocaine as a reinforcer, and (ii) to enable investigation of the neural mechanisms by which arbitrary cues gain motivational salience and, as conditioned reinforcers, control over drug-seeking behaviour. Initially, each infusion of cocaine was made contingent upon a response on ...

RATIONALE: γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA(B) receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA(B) receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA(B) receptor ...