Efficacy and side effects of baclofen and the novel GABA receptor positive allosteric modulator CMPPE in animal models for alcohol and cocaine addiction.

Rationale: Preclinical studies suggest that the GABA receptor is a potential target for treatment of substance use disorders. However, recent clinical trials report adverse effects in patients treated with the GABA receptor agonist baclofen and even question efficacy. How can the discrepancy between preclinical and clinical findings be explained?

Objective: To test efficacy and adverse effects of baclofen and the novel GABA positive allosteric modulator (PAM) CMPPE in rat addiction models, which were developed in accordance with DSM.

mGlu1 receptor as a drug target for treatment of substance use disorders: time to gather stones together?

Modulation of the mGlu1 receptor was repeatedly shown to inhibit various phenomena associated with exposure to abused drugs. Efficacy in preclinical models was observed with both positive and negative allosteric modulators (PAMs and NAMs, respectively) using essentially non-overlapping sets of experimental methods. Taken together, these data indicate that the mGlu1 receptor certainly plays a significant role in the plasticity triggered by the exposure to abused drugs and is involved in the maintenance of drug-seeking and drug-taking behaviors.

Morphine-induced Straub tail reaction in mice treated with serotonergic compounds.

Constitutively active 5-HT receptors have been suggested to contribute to motoneuronal excitability, muscle spasms and spasticity. Accordingly, 5-HT receptor inverse agonists have been demonstrated in pilot experiments to reduce spasticity in animal model of spasticity and patients with spinal cord injuries. Thus, 5-HT receptor inverse agonists may represent a novel class of anti-spasticity agents justifying a search for compounds with robust 5-HT receptor inverse agonist activity either among the existing medications or via a dedicated drug discovery program.

Agonist and antagonist effects of cytisine in vivo.

Varenicline, the most successful smoking cessation aid, is a selective partial agonists at α4β2* nicotinic receptors. Its efficacy is likely to be shared by other drugs with similar receptor action, including cytisine. The present study aimed to characterize behavioral effects of cytisine compared with nicotine using locomotor activity tests, intracranial self-stimulation of ventral tegmental area (discrete-trial threshold current intensity titration procedure), drug discrimination (0.

Effects of mGlu1 receptor blockade on working memory, time estimation, and impulsivity in rats.

Rationale: Metabotropic glutamate 1 (mGlu1) receptor antagonists were reported to induce cognitive deficits in several animal models using aversive learning procedures.

Objective: The present study aimed to further characterize behavioral effects of mGlu1 receptor antagonists using appetitively motivated tasks that evaluate working memory, timing, and impulsivity functions.

Materials And Methods: Separate groups of adult male Wistar rats were trained to perform four food-reinforced operant tasks: delayed non-matching to position (DNMTP), differential reinforcement of low rates of responding 18 s (DRL 18-s), signal duration discrimination (2-s vs 8-s bisection), and tolerance to delay of reward.

mGlu1 receptor blockade attenuates cue- and nicotine-induced reinstatement of extinguished nicotine self-administration behavior in rats.

Glutamatergic neurotransmission is believed to be critically involved in the acquisition and maintenance of drug addiction. The present study evaluated the role of metabotropic glutamate (mGlu) 1 receptors in the reinstatement of nicotine-seeking behavior. Rats were trained to nose-poke to receive response-contingent intravenous infusions of nicotine (0.

Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats.

Rationale: Metabotropic glutamate receptors (mGluRs) were reported to regulate various behavioral effects of addictive drugs.

Objective: The present study evaluated the role of group I mGluRs in the progressive augmentation ("sensitization") of the behavioral effects observed after repeated, intermittent cocaine exposure.

Materials And Methods: After habituation to handling and baseline activity measurement (days 1-2), rats received eight injections of cocaine (10 mg/kg) or saline on days 3-6, 8-11, and then, were tested twice with acute saline and cocaine given in a counterbalanced manner on days 13 and 15.

Metabotropic glutamate receptor (mGluR5) antagonist MPEP attenuated cue- and schedule-induced reinstatement of nicotine self-administration behavior in rats.

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.

Intravenous self-administration of abused solvents and anesthetics in mice.

Volatile organic solvents, fuels and anesthetics are subject to abuse. The aim of the present study was to evaluate i.v.