Involvement of the sigma1 receptor in the appetitive effects of cocaine.

Cocaine induces in the brain a drastic plasticity affecting numerous neurotransmission systems. In turn, the drug provokes a complex pattern of behavioral responses, including locomotor hyperactivity, stereotyped behaviors, sensitization, and appetitive and reinforcing properties that rapidly generate the addictive process. The involvement of sigma (1) receptors in cocaine effects has been suggested initially through the observation that sigma (1) antagonists could attenuate several acute effects induced by the drug, such as hyperlocomotion, stereotypies, convulsions and lethality. We will describe thereafter the recent results showing that activation of the sigma (1) receptor is also involved in the appetitive properties of cocaine, as measured using place preference conditioning in mice. Using selective sigma (1) antagonists or an in vivo antisense strategy, the role of the sigma (1) receptor in acquisition, expression and reactivation of conditioned place preference was demonstrated. The observation that repeated administration of cocaine rapidly provokes overexpression of the sigma (1) receptor outlines its major role in these first psychological steps of addictive processes. The physiological interaction between cocaine and sigma (1) receptors is detailed and the possibility that effective therapeutical strategies could target the sigma (1) receptor is considered.