Received for publication April 14, 2006.
Revised June 15, 2006.
Accepted for publication June 15, 2006.

Neonatal intrahippocampal gp120 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 HIV-1 protein gp120 were studied in vivo on prepulse inhibition (PPI) in adulthood. Further, the role of dopaminergic (DA) alterations was examined as a within-subjects factor. Using a randomized-block design, male and female pups of 8 Sprague-Dawley litters were injected bilaterally with either vehicle (VEH) (1µl volume) or gp120 (1.29, 12.9, or 129 ng/µl). At nine months of age, rats were injected subcutaneously with saline (SAL) (0.1ml/kg) and tested on preattentive processes, as indexed by sensorimotor gating. Sensorimotor gating was measured by PPI of the auditory startle response (ASR) (ISIs of 0, 8, 40, 80, 120, and 4000msec, 6 trial blocks, Latin-square design). One month later, the animals were treated with a D₁/D₂ agonist, apomorphine (APO) (0.1mg/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 4000msec). 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 (08-120msec) as the neonatal-injected gp120 dose increased. Use of APO to probe integrity of the DAergic system suggests long-lasting alterations in neuronal responses consequent to neonatal gp120 exposure.

Key words: D1/D2 agonist, HIV-1-associated dementia complex, apomorphine, gp120, hippocampus, prepulse inhibition