Neonatal intrahippocampal glycoprotein 120 injection: the role of dopaminergic alterations in prepulse inhibition in adult rats.
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.
Fitting
Sylvia
S
Department of Psychology, University of South Carolina, Columbia, SC 29208, USA. fitting@sc.edu
Booze
Rosemarie M
RM
Mactutus
Charles F
CF
D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015497:HIV-1 / Q000472:pathogenicity; D006624:Hippocampus / Q000187:drug effects*; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects*
D015699:HIV Envelope Protein gp120; D017447:Receptors, Dopamine D1; D016202:N-Methylaspartate; D001058:Apomorphine