Cocaine self-administration punished by intravenous histamine in adolescent and adult rats

Nathan A. Holtz, Marilyn E. Carroll

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)393-397
Number of pages5
JournalBehavioural Pharmacology
Issue number4
StatePublished - Jul 22 2015

Bibliographical note

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© 2015 Wolters Kluwer Health, Inc. All rights reserved.


  • adolescence
  • cocaine
  • histamine
  • punishment
  • rat
  • self-administration


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