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Reciprocal effects of response contingent and noncontingent intravenous heroin on in vivo nucleus accumbens shell versus core dopamine in the rat: a repeated sampling microdialysis study

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Abstract

Rationale

Although passive administration of heroin to drug-naive rats increases extracellular dopamine (DA) in the nucleus accumbens (NAc), its ability to do so also after active drug exposure (self-administration) is debated.

Objectives

This study investigated by repeated microdialysis sampling the inter- and intrasession changes in the responsiveness of the NAc shell and core DA and the behavioral effects of active and passive heroin exposure in the intravenous self-administration/yoked paradigm.

Materials and methods

Rats were implanted with jugular catheters and bilateral intracerebral chronic guide cannulae. Nose poking in the active hole by master rats resulted in heroin administration to the same subjects and to their yoked mates. Concentric microdialysis probes were inserted daily in the guide cannulae, and changes in dialysate DA in response to heroin exposure (0.05 mg/kg) were monitored in the same subject for 90 min for 4 weeks. Behavior associated with heroin exposure, distinguished into nonstereotyped and stereotyped, was also recorded.

Results

Dialysate DA increased preferentially in the shell of master rats from the first session (+112%) and throughout the 4 weeks of self-administration (+130–140%). In yoked rats, a preferential but lesser increase in DA in the shell was observed only on the first session (+60%), as the DA response in the NAc core increased progressively (+25–118%), so that within a week, the shell/core ratio was reversed, and this pattern was maintained for the following 2 weeks. Yoked rats showed a progressive and larger increase in stereotyped behaviors than master rats.

Conclusions

Chronic heroin self-administration increases extracellular DA preferentially in the NAc shell. Response-noncontingent heroin administration is particularly prone, compared to response-contingent administration, to induce behavioral and biochemical sensitization.

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Acknowledgments

The authors gratefully acknowledge the supply of the self-administration cages by Dr. Steve Goldberg and Dr. Gianluigi Tanda. This study was supported by funds from Ministero dell’Università e della Ricerca, progetti di Ricerca Nazionale Bando 2003, from the Centre of Excellence for Studies on the Neurobiology of the Addictions, and from the European Commission, NIDE project.

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Correspondence to Gaetano Di Chiara.

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Lecca, D., Valentini, V., Cacciapaglia, F. et al. Reciprocal effects of response contingent and noncontingent intravenous heroin on in vivo nucleus accumbens shell versus core dopamine in the rat: a repeated sampling microdialysis study. Psychopharmacology 194, 103–116 (2007). https://doi.org/10.1007/s00213-007-0815-y

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  • DOI: https://doi.org/10.1007/s00213-007-0815-y

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