Abstract
Considerable evidence suggests that psychostimulants can exert rewarding and locomotor-stimulating effects via increased dopamine transmission in the ventral striatum. However, the relative contributions of ventral striatal subregions to each of these effects have been little investigated. In the present study, we examined the contribution of different ventral striatal sites to the rewarding and locomotor-activating effects of cocaine. Initially, the effects of bilateral 6-hydroxydopamine lesions of the nucleus accumbens core or medial shell on cocaine-induced locomotor stimulation (0.5–1.5 mg/kg i.v. or 5–20 mg/kg i.p.) and conditioned place preference (0.5 mg/kg i.v. or 10 mg/kg i.p.) were examined. In a subsequent study, we investigated the effects of olfactory tubercle versus medial shell lesions on cocaine-conditioned place preference and locomotor activity (0.5 mg/kg i.v.). Dopaminergic lesion extent was quantified by radioligand binding to the dopamine transporter. Multiple linear regression was used to identify associations between behavioral effects and residual dopamine innervation in ventral striatal subregions. On this basis, the accumbens core was associated with the locomotor stimulant effects of i.v. and i.p. cocaine. In contrast, the medial shell was associated with the rewarding effect of i.v. cocaine, but not of i.p. cocaine. Finally, the olfactory tubercle was identified as an additional site contributing to conditioned place preference produced by i.v. cocaine. Overall, these findings provide additional evidence that the locomotor stimulant and rewarding effects of systemically administered psychomotor stimulant drugs are segregated within the ventral striatum.
Footnotes
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This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Institutes of Health Research. L.H.L.S. holds an NSERC Canada Graduate Scholarship.
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doi:10.1124/jpet.105.100339.
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ABBREVIATIONS: NAcc, nucleus accumbens; CPP, conditioned place preference; 6-OHDA, 6-hydroxydopamine; DAergic, dopaminergic; DA, dopamine; OT, olfactory tubercle; amOT, anteromedial olfactory tubercle; DAT, dopamine transporter; SERT, 5-hydroxytryptamine (serotonin) transporter; RTI-55, 3β-(4-iodophenyl)tropan-2-β-carboxylic acid methyl ester; GBR 12909; 1-{2-[bis(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine dihydrochloride; GBR 12935, 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride.
- Received December 20, 2005.
- Accepted February 27, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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