Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.

Many developmental syndromes have been linked to genetic mutations that cause abnormal ERK/MAPK activity; however, the neuropathological effects of hyperactive signaling are not fully understood. Here, we examined whether hyperactivation of MEK1 modifies the development of GABAergic cortical interneurons (CINs), a heterogeneous population of inhibitory neurons necessary for cortical function. We show that GABAergic-neuron specific MEK1 hyperactivation in vivo leads to increased cleaved caspase-3 labeling in a subpopulation of immature neurons in the embryonic subpallial mantle zone.

Chronic treatment with N-acetylcysteine decreases extinction responding and reduces cue-induced nicotine-seeking.

N-acetylcysteine (NAC), a promising glutamatergic therapeutic agent, has shown some clinical efficacy in reducing nicotine use in humans and has been shown to reverse drug-induced changes in glutamatergic neurophysiology. In rats, nicotine-seeking behavior is associated with alterations in glutamatergic plasticity within the nucleus accumbens core (NAcore). Specifically, cue-induced nicotine-seeking is associated with rapid, transient synaptic plasticity (t-SP) in glutamatergic synapses on NAcore medium spiny neurons.

Abuse liability of novel 'legal high' designer stimulants: evidence from animal models.

In the last few years, the variety and recreational use of 'legal high' designer stimulants has increased to unprecedented levels. Since their rapid emergence in drug markets, numerous adverse physical and psychological effects have been extensively reported. However, less is understood about the potential for compulsive use of and addiction to these drugs.

Protein kinase C isozymes as regulators of sensitivity to and self-administration of drugs of abuse-studies with genetically modified mice.

Studies using targeted gene deletion in mice have revealed distinct roles for individual isozymes of the protein kinase C (PKC) family of enzymes in regulating sensitivity to various drugs of abuse. These changes in drug sensitivity are associated with altered patterns of drug self-administration. The purpose of this review is to summarize behavioral studies conducted on mice carrying targeted deletions of genes encoding specific PKC isozymes (namely the beta, gamma, delta, and epsilon isozymes), and to critically evaluate the possibility of using pharmacological inhibitors of specific PKC isozymes as modulators of the sensitivity to various drugs of abuse, as well as potential aids in the treatment of substance use disorders.

Attenuation of cocaine-induced reinstatement of cocaine conditioned place preference by acamprosate.

Acamprosate (calcium acetylhomotaurinate) is a glutamatergic neuromodulator efficacious at reducing relapse in alcoholic patients. The effect of acamprosate on relapse to other drugs of abuse has received little attention, however, and given increasing evidence that glutamatergic transmission mediates relapse to cocaine-seeking behavior, the purpose of this study was to assess the effects of acamprosate on the reinstatement of a conditioned place preference for cocaine. Mice were conditioned daily with cocaine (15 mg/kg), tested for the establishment of cocaine conditioned place preference, and then retested once weekly to monitor the extinction of the place preference.