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Glutamate Transmission (glutamate + transmission)
Selected AbstractsA role for glutamate transmission in addiction to psychostimulantsADDICTION BIOLOGY, Issue 3 2000Peter W. Kalivas Psychostimulant addiction results in the emergence of undesirable behaviors such as drug craving and paranoia. Using animal models of addiction the neurobiological substrates mediating these behaviors have been examined. Studies have focused on cellular adaptations within the motive circuit that contains the nucleus accumbens, ventral tegmental area, ventral pallidum and prefrontal cortex. While long-term alterations in dopamine transmission have been clearly characterized, more recent studies reveal that important neuroadaptations are also produced in glutamate transmission. This short review provides a description of these neuroadaptations and a discussion of how these psychostimulant-induced changes may synergize to elicit addiction-related behaviors. [source] Chronic cocaine sensitizes striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Diego Centonze Abstract Behavioural studies indicate that cannabinoid receptors are implicated in cocaine addiction. The synaptic underpinning of cocaine,cannabinoid receptor interaction is however, obscure. We have studied electrophysiologically the sensitivity of cannabinoid receptors modulating synaptic transmission in the striatum of rats exposed to cocaine. One-day treatment with cocaine did not modify the synaptic response to HU210, a cannabinoid CB1 receptor agonist. Seven days cocaine-treatment, conversely, caused conditioned place preference, and sensitized striatal GABAergic synapses to the presynaptic effect of cannabinoid CB1 receptor stimulation. The cannabinoid receptor-induced modulation of glutamate transmission was unaltered by cocaine. Furthermore, the effects of chronic cocaine on cannabinoid-mediated regulation of striatal GABA synapses were attenuated one week after the discontinuation of cocaine, and absent two weeks later, indicating the progressive reversibility of the adaptations of cannabinoid system during abstinence of drug consumption. Our data support the concept that modulation of cannabinoid receptors might be useful against drug abuse. [source] Alterations in behaviour and glutamate transmission following presentation of stimuli previously associated with cocaine exposureEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001Gregory Hotsenpiller Abstract To study the role of glutamate in cocaine-conditioned responses, we developed a rat model in which conditioned locomotion is produced by repeated pairing of cocaine with discrete stimuli (flashing light and metronome). ,Paired' subjects received cocaine (15 mg/kg) prior to six exposures to stimuli for 30 min in the test environment. ,Unpaired' subjects received equivalent presentations of the stimuli yet received cocaine in home cages. Tests with the stimuli alone demonstrated that the conditioned locomotion displayed by Paired subjects was evident at 3 or 10 days post-training and resistant to two sessions of testing. The degree of conditioned locomotion was not correlated with the subjects' response to novelty or cocaine. Administration of the noncompetitive AMPA receptor antagonist GYKI 52466 (2.5 mg/kg, a dose without effect on spontaneous activity) attenuated the expression of conditioned activity. In vivo microdialysis revealed that Paired subjects had significantly lower basal glutamate levels in the nucleus accumbens (NAc) than did Unpaired subjects when no stimuli were presented. Presentation of the conditioned stimuli resulted in significant increases in glutamate levels in the NAc in the Paired group whilst glutamate levels in the Unpaired group remained unchanged. The associative control of glutamate levels in the NAc by stimuli formerly paired with a drug of abuse is an unprecedented finding. It is likely to reflect the convergence of excitatory inputs that the NAc receives from limbic structures. [source] Nigrostriatal denervation does not affect glutamate transporter mRNA expression but subsequent levodopa treatment selectively increases GLT1 mRNA and protein expression in the rat striatumJOURNAL OF NEUROCHEMISTRY, Issue 4 2001J.-C. Liévens There is growing evidence that the loss of the nigrostriatal dopaminergic neurones induces an overactivity of the corticostriatal glutamatergic pathway which seems to be central to the physiopathology of parkinsonism. Moreover, glutamatergic mechanisms involving NMDA receptors have been shown to interfere with the therapeutical action of levodopa. Given the key role played by uptake processes in glutamate neurotransmission, this study examined the effects of nigrostriatal deafferentation and of levodopa treatment on the striatal expression of the glutamate transporters GLT1, GLAST and EAAC1 in the rat. No significant changes in striatal mRNA levels of these transporters were detected after either levodopa treatment (100 mg/kg; i.p., twice a day for 21 days) or unilateral lesion of the nigrostriatal pathway by intranigral 6-hydroxydopamine injection. In contrast, animals with the lesion subsequently treated with levodopa showed a selective increase (36%) in GLT1 mRNA levels in the denervated striatum versus controls. These animals also showed increased GLT1 protein expression, as assessed by immunostaining and western blotting. These data provide the first evidence that levodopa therapy may interfere with striatal glutamate transmission through change in expression of the primarily glial glutamate transporter GLT1. We further suggest that levodopa-induced GLT1 overexpression may represent a compensatory mechanism preventing neurotoxic accumulation of endogenous glutamate. [source] | ||||||||||