Neurobehavioral alterations in HIV-1 transgenic rats: evidence for dopaminergic dysfunction.
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.
Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, SC 29208, USA. moranl@email.sc.edu
L M
LM
Moran
R M
RM
Booze
K M
KM
Webb
C F
CF
Mactutus
D015526:AIDS Dementia Complex / Q000235:genetics* / Q000523:psychology*; D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000502:physiology*; D005260:Female; D015497:HIV-1 / Q000235:genetics*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D008568:Memory / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013216:Reflex, Startle / Q000502:physiology; D055139:Sensory Gating / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine