TY - JOUR
T1 - Learning impairment following intracerebral administration of the HIV envelope protein gp120 or a VIP antagonist
AU - Glowa, John R.
AU - Panlilio, Leigh V.
AU - Brenneman, Douglas E.
AU - Gozes, Illana
AU - Fridkin, Mati
AU - Hill, Joanna M.
PY - 1992/1/20
Y1 - 1992/1/20
N2 - The external envelope glycoprotein (gp120) of the human immunodeficeincy virus (HIV) has been shown to be toxic to neurons in culture. To further investigate the neurological effects of gp120, the involvement of this protein with the acquisition of spatial discrimination was assessed. Both native and recombinant gp120 were administered into the cerebral ventricles of adult rats and performance was evaluated in the Morris swim maze. Gp120 treatment retarded acquisition after daily administration of 12 ng. The specificity of this impairment was demonstrated in that the performance of animals given the same amount of gp160 from recombinant baculovirus was not different from animals given saline. Vasoactive intestinal peptide (VIP) has been shown to block gp120-induced neurotoxicity in culture and a VIP receptor antagonist has displayed toxic properties to neurons in culture. We show here that this antagonist, which competitively inhibits VIP binding and blocks VIP-mediated functions in cell cultures from the CNS, also produced an impairment of performance. This retardation was attenuated by cotreatment with VIP, supporting the specificity of the observed impairment. Thus, gp120 and the VIP antagonist produced similar retardation of spatial discrimination, suggesting that both may impair memory for spatially related stimulus control.
AB - The external envelope glycoprotein (gp120) of the human immunodeficeincy virus (HIV) has been shown to be toxic to neurons in culture. To further investigate the neurological effects of gp120, the involvement of this protein with the acquisition of spatial discrimination was assessed. Both native and recombinant gp120 were administered into the cerebral ventricles of adult rats and performance was evaluated in the Morris swim maze. Gp120 treatment retarded acquisition after daily administration of 12 ng. The specificity of this impairment was demonstrated in that the performance of animals given the same amount of gp160 from recombinant baculovirus was not different from animals given saline. Vasoactive intestinal peptide (VIP) has been shown to block gp120-induced neurotoxicity in culture and a VIP receptor antagonist has displayed toxic properties to neurons in culture. We show here that this antagonist, which competitively inhibits VIP binding and blocks VIP-mediated functions in cell cultures from the CNS, also produced an impairment of performance. This retardation was attenuated by cotreatment with VIP, supporting the specificity of the observed impairment. Thus, gp120 and the VIP antagonist produced similar retardation of spatial discrimination, suggesting that both may impair memory for spatially related stimulus control.
KW - Autoimmune deficiency syndrome
KW - Dementia
KW - External envelope glycoprotein
KW - Human immunodeficiency virus
KW - Memory
KW - Vasoactive intestinal peptide
UR - http://www.scopus.com/inward/record.url?scp=0026546845&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(92)90562-N
DO - 10.1016/0006-8993(92)90562-N
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AN - SCOPUS:0026546845
SN - 0006-8993
VL - 570
SP - 49
EP - 53
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -
