Sigma(1) (sigma(1)) receptor antagonists represent a new strategy against cocaine addiction and toxicity
by
Maurice T, Martin-Fardon R, Romieu P, Matsumoto RR.
CNRS UMR 5102, University of Montpellier II, c.c. 090,
place Eugene Bataillon,
34095 Montpellier cedex 5, France.
maurice@univ-montp2.fr
Neurosci Biobehav Rev 2002 Jun;26(4):499-527


ABSTRACT

Cocaine is a highly addictive substance abused worldwide. Its mechanism of action involves initially inhibition of neuronal monoamine transporters in precise brain structures and primarily the dopamine reuptake system located on mesolimbic neurons. Cocaine rapidly increases the dopaminergic neurotransmission and triggers adaptive changes in numerous neuronal circuits underlying reinforcement, reward, sensitization and the high addictive potential of cocaine. Current therapeutic strategies focus on counteracting the cocaine effects directly on the dopamine transporter, through post-synaptic D(1), D(2) or D(3) receptors or through the glutamatergic, serotoninergic, opioid or corticotropin-releasing hormone systems. However, cocaine administration also results in the activation of numerous particular targets. Among them, the sigma(1) (sigma(1)) receptor is involved in several acute or chronic effects of cocaine. The present review will first bring concise overviews of the present strategies followed to alleviate cocaine addiction and animal models developed to analyze the pharmacology of cocaine addiction. Evidence involving activation of the sigma(1) receptor in the different aspects of cocaine abuse, will then be detailed, following acute, repeated, or overdose administration. The therapeutic potentials and neuropharmacological perspectives opened by the use of selective sigma(1) receptor antagonists in cocaine addiction will finally be discussed.


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Monoamines, cocaine and rats
Cocaine and artificial enzymes
Freebasing flies go hyperkinetic
Cocaine and the sigma 1 receptors
Sigma agonists as antidepressants: igmesine
Do sigma1 agonists like igmesine make cocaine more rewarding?

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