Alteration of Methamphetamine-induced stereotypic behaviour in transgenic mice expressing HIV-1 envelope protein gp120

Abstract

The use of drugs for recreational purposes, in particular Methamphetamine, is associated with an increased risk of infection with human immunodeficiency virus (HIV)-1. HIV-1 infection in turn can lead to HIV-associated neurological disorders (HAND) that range from mild cognitive and motor impairment to HIV-associated dementia (HAD). Interestingly, post mortem brain specimens from HAD patients and transgenic (tg) mice expressing the viral envelope protein gp120 in the central nervous system display similar neuropathological signs. In HIV patients, the use of Methamphetamine appears to aggravate neurocognitive alterations. In the present study, we injected HIV/gp120tg mice and non-transgenic littermate control animals with Methamphetamine dissolved in Saline or Saline vehicle and assessed locomotion and stereotyped behaviour. We found that HIVgp120-transgenic mice differ significantly from non-transgenic controls in certain domains of their behavioural response to Methamphetamine. Thus this experimental model system may be useful to further study the mechanistic interaction of both the viral envelope protein and the psychostimulant drug in behavioural alterations and neurodegenerative disease.

Figure 1

Activity and stereotyped behaviour of HIV/gp120 transgenic and non-transgenic littermate control mice after i.p. injection of different doses of Methamphetamine or Saline vehicle. Age-matched 9 to 13 month-old HIV/gp120tg mice (5 females, 5 males) and non-transgenic littermate control animals (7 females, 3 males) were injected i.p. with Saline (vehicle control) or Methamphetamine at the indicated concentration. Subsequently locomotion and stereotyped behaviour was assessed by visual observation (A) and automated recording (B) as described in the text. * adjusted p < 0.05 for differences between genotypes, • adjusted p < 0.05 for differences between Saline and Methamphetamine treatments.