RESUMO
Between 30 and 60% of HIV-seropositive individuals develop symptoms of clinical depression and/or apathy. Dopamine and serotonin are associated with motivational alterations; however, histamine is less well studied. In the present study, we used fast-scan cyclic voltammetry in HIV-1 transgenic (Tg) rats to simultaneously analyze the kinetics of nucleus accumbens dopamine (DA), prefrontal cortical serotonin (5-HT), and hypothalamic histamine (HA). For voltammetry, subjects were 15 HIV-1 Tg (7 male, 8 female) and 20 F344/N (11 male, 9 female) adult rats. Both serotonergic and dopaminergic release and reuptake kinetics were decreased in HIV-1 Tg animals relative to controls. In contrast, rates of histamine release and reuptake increased in HIV-1 Tg rats. Additionally, we used immunohistochemical (IHC) methods to identify histaminergic neurons in the tuberomammillary nucleus (TMN) of the hypothalamus. For IHC, subjects were 9 HIV-1 Tg (5 male, 4 female) and 9 F344/N (5 male, 4 female) adult rats. Although the total number of TMN histaminergic cells did not differ between HIV-1 Tg rats and F344/N controls, a significant sex effect was found, with females having an increased number of histaminergic neurons, relative to males. Collectively, these findings illustrate neurochemical alterations that potentially underlie or exacerbate the pathogenesis of clinical depression and/or apathy in HIV-1.
Assuntos
Dopamina/metabolismo , HIV-1/genética , Histamina/metabolismo , Hipotálamo/metabolismo , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Serotonina/metabolismo , Animais , Apatia , Depressão/metabolismo , Depressão/psicologia , Depressão/virologia , Feminino , Infecções por HIV/metabolismo , Infecções por HIV/psicologia , Infecções por HIV/virologia , HIV-1/metabolismo , Hipotálamo/virologia , Masculino , Modelos Biológicos , Núcleo Accumbens/virologia , Córtex Pré-Frontal/virologia , Ratos , Ratos Endogâmicos F344 , Ratos Transgênicos , Fatores Sexuais , Transmissão Sináptica , Proteínas Virais/biossíntese , Proteínas Virais/genéticaRESUMO
HIV-1 and addictive drugs, such as cocaine (COC), may act in combination to produce serious neurological complications. In the present experiments, striatal brain slices from HIV-1 transgenic (Tg) and F344 control female rats were studied. First, we examined dopamine (DA) reuptake in control, HIV-1, COC-treated (5µM) and HIV-1+COC-treated, striatal slices using fast scan cyclic voltammetry. COC-treated striatal slices from F344 control animals significantly increased DA reuptake time (T80), relative to untreated control slices. In contrast, in HIV-1 Tg striatal slices, DA reuptake time was extended by HIV-1, which was not further altered by COC treatment. Second, analysis of medium spiny neuronal populations from striatal brain slices found that controls treated with cocaine displayed increases in spine length, whereas cocaine treated HIV-1 slices displayed decreased spine length. Taken together, the current study provides evidence for dysfunction of the dopamine transporter (DAT) in mediating DA reuptake in HIV-1 Tg rats and limited responses to acute COC exposure. Collectively, dysfunction of the DAT reuptake and altered dendritic spine morphology of the MSNs, suggest a functional disruption of the dopamine system within the HIV-1 Tg rat.
Assuntos
Cocaína/farmacologia , Corpo Estriado/citologia , Dopamina/metabolismo , HIV-1/fisiologia , Neurônios/metabolismo , Animais , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/metabolismo , Feminino , Neurônios/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ratos Endogâmicos F344 , Ratos TransgênicosRESUMO
HIV-1 associated neurocognitive deficits are increasing in prevalence, although the neuronal basis for these deficits is unclear. HIV-1 Tg rats constitutively express 7 of 9 HIV-associated proteins, and may be useful for studying the neuropathological substrates of HIV-1 associated neurocognitive disorders (HAND). In this study, adult female HIV-1 Tg rats and F344 control rats had similar growth rates, estrous cyclicity and startle reflex inhibition to a visual prepulse stimulus. Medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) were ballistically-labeled utilizing the indocarbocyanine dye DiI. The branching complexity of MSNs in the NAcc was significantly decreased in HIV-1 Tg rats, relative to controls; moreover, the shorter length and decreased volume of dendritic spines, but unchanged head diameter, in HIV-1 Tg rats suggested a reduction of longer spines and an increase in shorter, less projected spines, indicating a population shift to a more immature spine phenotype. Collectively, these results from HIV-1 Tg female rats indicated significant synaptodendritic alterations of MSNs in the NAcc occur as a consequence of chronic, low-level, exposure to HIV-1 associated proteins.
