Regulation of [3H]dopamine release from mesolimbic and mesocortical areas of guinea pig brain by sigma receptors

Document Type

Journal Article

Publication Date



Schizophrenia Research








(+)Pentazocine; BD737; Dopamine; Nucleus accumbens; Prefrontal cortex; Sigma


The role of sigma (σ) receptors in brain function is poorly defined. They are located in limbic areas, including nucleus accumbens (NAC) and prefrontal cortex (PFC), both of which are thought to be involved in schizophrenia. Many antipsychotics (APs), including haloperidol, bind with high affinity to a receptors. Dopaminergic hyperactivity in NAC is thought to underlie positive symptoms of schizophrenia, while dopaminergic hypoactivity in PFC is thought to underlie negative symptoms. Sigma receptors regulate N- methyl-D-ASPARTATE (NMDA)-STIMULATED [3H]dopamine ([3H]DA) release in caudate-putamen (CP), the neuroanatomical substrate for extrapyramidal side effects resulting from chronic AP treatment. In the current study, we investigated whether σ receptors could similarly regulate DA release in mesolimbic and mesocortical tissue, and the relative participation of different a receptor subtypes in this process. We found that, in NAC, regulation of DA release by the prototypical σ agonist (+)pentazocine was mediated predominantly by the σ1 receptor, whereas in the PFC a portion of the (+)pentazocine effect was likely mediated by the σ2 receptor. We also observed, in both the NAC and PFC, that regulation of DA release by the a agonist BD737 was mediated primarily by the σ1 receptor. In addition, we determined that (+)pentazocine or BD737 effects on DA release were not mediated via opioid receptors, nor the phencyclidine (PCP) binding site within the NMDA receptor-operated cation channel, nor by σ receptor effects upon [3H]DA accumulated by noradrenergic terminals in PFC.

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