Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

Kesby, James P., Hubbard, David T., Markou, Athina and Semenova, Svetlana (2014) Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice. Addiction Biology, 19 4: 593-605. doi:10.1111/adb.12023


Author Kesby, James P.
Hubbard, David T.
Markou, Athina
Semenova, Svetlana
Title Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice
Journal name Addiction Biology   Check publisher's open access policy
ISSN 1369-1600
1355-6215
Publication date 2014-07
Year available 2012
Sub-type Article (original research)
DOI 10.1111/adb.12023
Open Access Status Not yet assessed
Volume 19
Issue 4
Start page 593
End page 605
Total pages 13
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population.
Keyword Conditioned place preference
Food-maintained responding
Oral self-administration
Pharmacokinetics
Quinine
Saccharin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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