Neurobehavioral alterations in HIV-1 transgenic rats: Evidence for dopaminergic dysfunction

• Published in: Experimental neurology 2013-01, Vol.239, p.139-147
• Main Authors: Moran, L.M., Booze, R.M., Webb, K.M., Mactutus, C.F.
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Addictive behaviors; Adult and adolescent clinical studies; AIDS; AIDS Dementia Complex - genetics; AIDS Dementia Complex - psychology; Analysis of Variance; Animals; Behavior, Animal - physiology; Biological and medical sciences; Body Weight - physiology; Cocaine - pharmacology; Cocaine sensitization; Dopamine; Dopamine Uptake Inhibitors - pharmacology; Dopaminergic Neurons - physiology; Drug addiction; Female; Habituation; Habituation, Psychophysiologic - physiology; HAND; HIV-1 - genetics; HIV-1 transgenic rat; Human viral diseases; Infectious diseases; Medical sciences; Memory - physiology; Motor Activity - physiology; Neurology; Novelty; Ovariectomy; Prepulse inhibition; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Reflex, Startle - physiology; Retention; Sensorimotor gating; Sensory Gating - physiology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2012.10.008

Clinical studies have provided evidence that the progression of HIV-1-associated neurocognitive disorders (HAND) involves alterations in dopamine (DA) systems. Drugs of abuse that act on the brain DA system, such as cocaine (Coc), may exacerbate HIV-1 infection and consequent behavioral and neurological manifestations. In the present study, we used the HIV-1 transgenic (Tg) rat, which constitutively expresses 7 of the 9 HIV-1 genes, to assess potential DA system alterations in three behavioral assays: prepulse inhibition (PPI) of the auditory startle response (ASR), novelty and habituation/retention, and sensitization to Coc across repeated administration. Adult female Sprague–Dawley rats were tested in each experiment. The HIV-1 Tg animals were hyperreactive to auditory startle stimuli and displayed a leftward shift in the temporal window for maximal PPI, suggesting an alteration in sensorimotor gating. All animals displayed an initial robust locomotor response to a novel environment which dissipated with repeated testing; however, the HIV-1 Tg rats, relative to controls, consistently showed a weaker novelty response across monthly-spaced assessments. The HIV-1 Tg animals also showed decreased intrasession habituation of motor activity across 3-day periods that emerged across monthly-spaced locomotor activity sessions; a pattern consistent with impaired long-term episodic memory. Furthermore, the HIV-1 Tg group displayed differential cocaine-induced sensitization, observed both in initiation across the 10-day cocaine treatment, and in expression following a cocaine rechallenge after a 7-day abstinence. Collectively, the present data implicate that the non-infectious HIV-1 Tg rat, which resembles the complete suppression of infection in HIV-1 positive individuals under CART, displays sustained, if not permanent, alterations in the brain DA system. ► HIV-1 Tg rats show altered PPI, novelty response, habituation and Coc sensitization. ► Deficits were prior to any noted neurological symptoms or clinical signs of wasting. ► Alterations in the DA system are implicated in the non-infectious HIV-1 Tg rat.