Intrahippocampal injections of Tat: Effects on prepulse inhibition of the auditory startle response in adult male rats

Abstract

The presence of human immunodeficiency virus (HIV-1) in the brain mediates the pathogenesis of HIV-associated dementia complex (HAD), partially through the viral toxins gp120 and Tat. This study characterized potential deficits in sensorimotor gating, as measured by prepulse inhibition (PPI), following hippocampal administration of Tat. Adult, male Sprague–Dawley rats were bilaterally injected with 50 μg Tat or saline (1 μl volume), into the hippocampus. Following 7 weeks of recovery, all animals were tested using the auditory startle response (ASR) with habituation, control, and PPI trials. Assessment of ASR habituation [100dB(A) white noise stimulus, 70dB(A) background, 5-min acclimation period, 36 habituation trials with fixed interstimulus interval (ISI) of 10 s] demonstrated a significant ∼ 50% reduction in the overall peak ASR amplitude, but no change in peak ASR latency, nor an effect on the rate of habituation. PPI measures demonstrated robust alterations in sensorimotor gating. The PPI test (ISI of 0, 8, 40, 80, 120, or 4000 ms, 6-trial blocks, Latin-square) showed an attenuated response on peak ASR amplitude during the control trials (0 and 4000 ms ISI), but not on the PPI trials (8–120 ms ISI). Most striking was the rightward shift in ISI for maximal inhibition of the response ( χ 2(1) = 4.7, p ≤ 0.03). There was no significant peak ASR latency effect during the control trials (< 1 ms) of the PPI test, although there was the suggestion of a slowing of the response (4 ms, ∼ 15%) across PPI trials. Collectively, the present data suggest that intrahippocampal injections of Tat have adverse effects on cognitive processing, as indexed by sensorimotor gating.