Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The involvement of the sigma(1) receptor on the rewarding effects of cocaine was examined using the conditioned place preference (CPP) procedure in C57BL/6 mice. Acquisition or expression of cocaine (20 mg/kg i.p.)-induced CPP was significantly decreased by pre-treatment with the selective sigma(1) receptor antagonists N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine (NE-100) or N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047), 1-10 mg/kg, i.p. The sigma(1) receptor agonists igmesine or 2-(4-morpholinoethyl-1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084) failed to induce CPP when injected alone. Moreover, the CPP induced by N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP), a selective dopamine reuptake inhibitor, was blocked by treatments with the sigma(1) receptor antagonists as was similarly observed with cocaine. In addition, the repetitive treatment with cocaine during conditioning increased sigma(1) receptor mRNA expression in the nucleus accumbens, but not in the caudate putamen, prefrontal cortex or cerebellum. These data show that the sigma(1) receptor is not only necessary for acquisition of the cocaine-induced CPP, but that it is also implicated in its expression, confirming that activation of the sigma(1) receptor is induced during cocaine's early effects. The sigma(1) receptor is activated consequently to dopamine reuptake blockade and is not sufficient to induce CPP by itself. The mechanism of the sigma(1) receptor involvement in CPP and the selectivity toward the CPP-inducing drug remains however to be determined. These results show that strategies targeting the sigma(1) receptor with selective antagonists may allow effective attenuation of cocaine's rewarding properties and, in turn, offer new treatment strategies against drug addiction.
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PMID:Involvement of the sigma(1) receptor in cocaine-induced conditioned place preference: possible dependence on dopamine uptake blockade. 1192 69

This study utilised the two injection protocol of sensitisation (TIPS) and the conditioned place preference test to validate and extend previous findings on the effects of amphetamine on positive reinforcement-related 50 kHz ultrasonic vocalisation (USV) in rats. We also examined changes in the expression of c-Fos and the NMDA receptor 2B (GluN2B) subunit, markers of neuronal activity and plasticity, in brain regions of rats in response to TIPS. We used low anxiety-responsive (LR) and high anxiety-responsive (HR) rats, which are known to exhibit different fear-conditioned response strengths, different susceptibilities to amphetamine in the TIPS procedure and different amphetamine-dependent 50 kHz USV responses. The LR rats, compared to the HR rats, not only vocalised much more intensely but also spent significantly more time in the amphetamine-paired compartment. After the second dose of amphetamine, the LR rats exhibited more c-Fos and GluN2B activation in layers II and III of the M1/M2 motor cortex area and prefrontal cortex (PRE, PRL, IL) and also presented with more GluN2B activation in the basal amygdala. These data reveal that HR and LR rats exhibit different levels of reactivity in the cortical-limbic pathway, which controls reward-related motivational processes. These findings contribute to the general hypothesis that heterogeneity in emotional processes is one of the causes of sensitisation to amphetamine and drug addiction.
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PMID:Low-anxiety rats are more sensitive to amphetamine in comparison to high-anxiety rats. 2770 43