title: Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat.
abstract: BACKGROUND
  In naive rats, passive administration of drugs of abuse preferentially increases extracellular dopamine (DA) in the nucleus accumbens (NAc) shell as compared to the core. Repeated exposure to the same drugs results in behavioral and biochemical sensitization characterized by stereotyped activity and reduction of the shell/core DA response ratio.
  
  
  OBJECTIVE
  The aim of this work is to study the neurochemical and behavioral effects of response-contingent vs response-noncontingent drug administration in rats, who were bilaterally implanted with chronic intracerebral guide cannulae and trained to self-administer cocaine by nose poking in daily 1-h sessions for 3 weeks (5 days/week). Nose poking in the active hole by master rats resulted in intravenous injection of cocaine (0.25 mg/kg) in master rats and in rats yoked to them. Dialysate DA was monitored before, during, and for 30 min after cocaine availability on alternate days by inserting the probe into the NAc shell and core. Stereotyped and non-stereotyped behavior was recorded during the sessions.
  
  
  RESULTS
  In master rats, dialysate DA increased preferentially in the NAc shell during cocaine self-administration throughout the 3 weeks of cocaine exposure. In yoked rats, DA increased preferentially in the shell but to a lesser extent than in master rats. With continued exposure to cocaine, the shell/core ratio of DA changes decreased progressively and, on the third week, was reversed so that DA increased more in the core than in the shell. Yoked rats showed a progressive and faster increase in stereotyped behaviors than master rats.
  
  
  CONCLUSIONS
  Response-noncontingent cocaine administration is particularly prone, compared to response-contingent administration, to induce behavioral and biochemical sensitization.
authors.affiliation: Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lecca
authors.forename: Fabio
authors.initials: F
authors.lastname: Cacciapaglia
authors.forename: Valentina
authors.initials: V
authors.lastname: Valentini
authors.forename: Elio
authors.initials: E
authors.lastname: Acquas
authors.forename: Gaetano
authors.initials: G
authors.lastname: Di Chiara
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological; D007262:Infusions, Intravenous; D008124:Locomotion / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012646:Self Administration; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D003042:Cocaine; D004298:Dopamine