title: Cocaine self-administration punished by intravenous histamine in adolescent and adult rats.
abstract: Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Holtz
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Carroll
mesh_terms: D061605:Administration, Intravenous; D000375:Aging; D000818:Animals; D021461:Animals, Outbred Strains; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000503:physiopathology; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006632:Histamine / Q000008:administration & dosage*; D017442:Histamine Agonists / Q000008:administration & dosage*; D023421:Models, Animal; D011678:Punishment; D017208:Rats, Wistar; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D017442:Histamine Agonists; D006632:Histamine; D003042:Cocaine