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.
BACKGROUND
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.


OBJECTIVE
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.


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.
Lecca
Daniele
D
Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
Valentini
Valentina
V
Cacciapaglia
Fabio
F
Acquas
Elio
E
Di Chiara
Gaetano
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015314:Dialysis Solutions / Q000032:analysis / Q000737:chemistry; D004298:Dopamine / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D003932:Heroin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007120:Immunochemistry; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis / Q000379:methods*; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013997:Time Factors
D015314:Dialysis Solutions; D009294:Narcotics; D003932:Heroin; D004298:Dopamine