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BEHAVIORAL PHARMACOLOGY

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

Department of Psychology, University of South Carolina, Columbia, South Carolina

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 µl volume) or gp120 (1.29, 12.9, or 129 ng/µl). 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 D₁/D₂ 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.

Address correspondence to: Sylvia Fitting, Department of Psychology, University of South Carolina, 1512 Pendleton Street, Columbia, SC 29208. E-mail: fitting{at}sc.edu.