Adolescent HIV-1 transgenic rats: evidence for dopaminergic alterations in behavior and neurochemistry revealed by methamphetamine challenge.
Curr HIV Res
; 10(5): 415-24, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22591365
ABSTRACT
Since the introduction of combination antiretroviral therapy (cART) in the mid-90s, the most severe forms of HIV-1-associated neurocognitive disorders (HAND) have diminished. However, milder forms of HAND remain prevalent. Basic and clinical studies implicate alterations in the dopaminergic (DAergic) system in HIV-1 infection. We used the Fischer 344 HIV-1 transgenic (HIV-1 Tg) rat, which expresses 7 of the 9 HIV-1 genes, to examine potential DAergic alterations. Animals were studied beginning at 35 days of age to assess early-onset DAergic alterations, well before any documented neurological symptoms or clinical signs of "wasting". At 48 hr intervals, animals were administered a single dose of methamphetamine (METH) (0, 0.5, 1, 2.5 and 5 mg/kg/ml s.c.) and tested for the auditory startle response (ASR) and prepulse inhibition (PPI), using an auditory prepulse [85 dB(A) broad-band noise stimulus] and an auditory startle stimulus [100 dB(A) broad-band noise stimulus] in a sound-attenuating chamber with a continuous 70 dB(A) white noise background. The protocol used a 5-min acclimation period, 6 startle trials, and 36 PPI trials [ISIs of 0, 8, 40, 80, 120, and 4000 ms, 6-trial blocks, Latin square design]. As the dose of METH increased, PPI of the startle response decreased. The HIV-1 Tg rats displayed a greater dose-dependency to the METH-induced disruption of PPI compared to non-transgenic controls. Western blot analysis of midbrain extracts revealed lower tyrosine hydroxylase (TH) protein levels and higher monoamine oxidase A (MAO-A) protein levels in HIV-1 Tg rats treated with METH compared to non-transgenic controls. Early-detected cognitive alterations in the preattentive process of sensorimotor gating may have significant predictive utility regarding the progression of DAergic alterations in HIV-1 infection.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reflexo de Sobressalto
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Mesencéfalo
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Dopamina
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HIV-1
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Estimulantes do Sistema Nervoso Central
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Metanfetamina
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Revista:
Curr HIV Res
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos