RATIONALE: 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. OBJECTIVES: 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). CONCLUSION: 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.
RATIONALE: 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. OBJECTIVES: 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). CONCLUSION: 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.
Authors: Herbert E Covington; Thomas F Tropea; Anjali M Rajadhyaksha; Barry E Kosofsky; Klaus A Miczek Journal: Psychopharmacology (Berl) Date: 2007-12-19 Impact factor: 4.530
Authors: Yong Zhang; Stefan D Schlussman; Eduardo R Butelman; Ann Ho; Mary Jeanne Kreek Journal: Neuropharmacology Date: 2012-04-04 Impact factor: 5.250
Authors: Yan Zhou; Yoav Litvin; Anna Paola Piras; Donald W Pfaff; Mary Jeanne Kreek Journal: Neuropsychopharmacology Date: 2011-06-15 Impact factor: 7.853
Authors: Yong Zhang; Stefan D Schlussman; Jacqui Rabkin; Eduardo R Butelman; Ann Ho; Mary Jeanne Kreek Journal: Neuropharmacology Date: 2012-11-16 Impact factor: 5.250