Differential neurochemical and behavioral responses induced by contingent and non-contingent heroin administration

LECCA, DANIELE;Cacciapaglia F;VALENTINI, VALENTINA;Di Chiara G.

2006-01-01

---

Abstract

In naive rats, passive administration of drugs of abuse preferentially increases extracellular dopamine (DA) levels in the nucleus accumbens (NAc) shell as compared to the core. Repeated exposure to the same drugs results in the induction of behavioral and biochemical sensitization characterized by stereotyped activity and by reduction of the DA shell/core response ratio. To date, no information is available on the within subject evolution of the response of DA transmission across the daily sessions of heroin drug SA. This study was aimed to investigate the changes of extracellular DA in the NAc shell and core of rats, along with the behavioral responses, during response-contingent and non-contingent intravenous heroin administration. Rats were implanted with a catheter in the right jugular vein and bilaterally with intracerebral chronic cannulae aimed at the NAc shell and core. After recovery, rats were trained to self-administer heroin in single daily 1h-session for four weeks (5 days/weeks). Nose-pokes in the active hole resulted in intravenous injection of heroin (0.05 mg/kg) to master (response contingent) and yoked (non-contingent administration) rats. Dialysate DA was monitored for 90-min after each session from the NAc shell and core starting on the first exposure to the drug. Behavioral effects of contingent and non-contingent drug exposure, distinguished into non-stereotyped and stereotyped activity was recorded. No differences were found in basal extracellular DA in the NAc shell and core. DA levels elicited by heroin in the NAc of master rats were greater in the shell compared to the core, whereas, in yoked rats the DA shell and core responsiveness was similar during the first week and became higher in the core compared to the shell from the second week until the end of heroin paired-administered. Moreover, yoked rats showed a progressive and faster increase of stereotyped behaviors than master rats. Non-stereotyped behavior followed the reverse trend. Response-non-contingent heroin administration is particularly prone, compared to response-contingent administration, to induce behavioral and neurochemical sensitization.