Differential neurochemical and behavioral adaptation to cocaine after response contingent and noncontingent exposure in the rat |
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Authors: | Daniele Lecca Fabio Cacciapaglia Valentina Valentini Elio Acquas Gaetano Di Chiara |
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Institution: | (1) Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy;(2) Centre of Excellence for Studies on the Neurobiology of Addiction, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy;(3) Institute of Neuroscience, Consiglio Nazionale delle Ricerche (CNR), Section of Cagliari, Cagliari, Italy |
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Abstract: | Rationale 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.
Objectives 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. |
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Keywords: | Self-administration Master rats Yoked rats Microdialysis Cocaine Dopamine Nucleus accumbens shell Nucleus accumbens core Non-stereotyped behavior Stereotyped behavior |
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