A GOLDFISH MODEL FOR EVALUATION OF THE NEUROTOXICITY OF OMEGA-CONOTOXIN GVI-A AND SCREENING OF MONOCLONAL-ANTIBODIES

The neurotoxicity of ω-conotoxin (ω-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. ω-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. ω-CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antibodies was investigated in vivo by either (1) preincubation of the antibody with ω-CgTx at 4°C overnight, or (2) pretreatment with antibody, 30 min before ω-CgTx injection in a 10:1 antibody/ω-CgTx molar ratio. The LD50 dose of ω-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with ω-CgTx (5 nmol/kg ip) significantly (p < 0.05) reduced mortality, ASB, and toxicity time. The antitoxin activity of the monoclonal antibodies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by ω-CgTx (0.03 nmol/rat icv) were significantly (p < 0.02 and p < 0.01, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple, accurate, and inexpensive in vivo model for the study of the toxicity of ω-CgTx. © 1991.