Dose preference and dose escalation in extended-access cocaine self-administration in Fischer and Lewis rats.
BACKGROUND
Drug addiction is a disease with a genetic component that may be involved in different stages of its progression. Cocaine users escalate unit doses and frequency of self-administration events in naturalistic settings. Rats that self-administer drugs of abuse over extended sessions increase the number of infusions over days.


OBJECTIVE
Comparison of two genetically different inbred rat strains, Fischer and Lewis, in a new self-administration paradigm whereby rats select between different unit doses of cocaine, thus potentially escalating the unit dose and the number of infusions.


METHODS
Extended (18 h/day) self-administration sessions lasted for 14 days. Rats had access to two active levers associated with two different unit doses of cocaine. If a rat showed preference for the higher unit dose, then the available doses were escalated in the following session. Four cocaine unit doses were available (0.2, 0.5, 1.25, and 2.5 mg/kg/infusion).


RESULTS
Lewis rats showed a clear preference for the two higher doses of cocaine (70% of rats), with a high percentage (35%) of the individuals escalating to the highest unit dose, and escalated the total amount of cocaine taken over days. Fischer rats, however, preferred the two lower doses (63%) and did not escalate the amount of cocaine taken over days. Fischer, but not Lewis, rats showed an activated hypothalamic-pituitary-adrenal axis in acute withdrawal (24 h).


CONCLUSIONS
This work shows the power of a model of extended-access self-administration that allows for the subject-controlled dose-escalation of the unit dose of cocaine, and underlines the genetic differences that modulate cocaine intake.
Picetti
Roberto
R
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, Box 171, New York, NY 10065, USA. rpicetti@rockefeller.edu
Ho
Ann
A
Butelman
Eduardo R
ER
Kreek
Mary Jeanne
MJ
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344 / Q000523:psychology*; D011917:Rats, Inbred Lew / Q000523:psychology*; D012646:Self Administration; D013045:Species Specificity
D000324:Adrenocorticotropic Hormone; D003042:Cocaine; D003345:Corticosterone