Neonatal Intrahippocampal Glycoprotein 120 Injection: The Role of Dopaminergic Alterations in Prepulse Inhibition in Adult Rats

Abstract

Following neonatal hippocampal administration on postnatal day 1, the dose-response effects of the human immunodeficiency virus 1 protein glycoprotein 120 (gp120) were studied in vivo on prepulse inhibition (PPI) in adulthood. Furthermore, the role of dopaminergic alterations was examined as a within-subject factor. Using a randomized-block design, male and female pups of eight Sprague-Dawley litters were injected bilaterally with either vehicle (1 microl volume) or gp120 (1.29, 12.9, or 129 ng/microl). At 9 months of age, rats were injected s.c. with saline (SAL) (0.1 ml/kg) and tested on preattentive processes, as indexed by sensorimotor gating. Sensorimotor gating was measured by PPI of the auditory startle response (ASR) [interstimulus intervals (ISIs) of 0, 8, 40, 80, 120, and 4000 ms, six trial blocks, Latin square design]. One month later, the animals were treated with a D(1)/D(2) agonist, apomorphine (APO) (0.1 mg/kg) and again tested for PPI. A significant attenuation of the baseline ASR by APO was noted. No significant effects were noted on control ASR trials (ISIs, 0 and 4000 ms). For the SAL condition, response inhibition was significantly reduced as a function of gp120 dose, and the inflection of the inhibition curve was significantly altered for the high-gp120 dose-treated animals. A gp120 treatment x APO drug interaction was evident on amplitude, but not latency, of the response inhibition, with an enhanced inhibition in the APO condition, collapsed across ISIs (08-120 ms) as the neonatal-injected gp120 dose increased. Use of APO to probe integrity of the dopaminergic system suggests long-lasting alterations in neuronal responses consequent to neonatal gp120 exposure.