Distribution of N-type Ca2+ channel binding sites in rabbit brain following central administration of omega-conotoxin GVIA

Central administration of the N-type Ca2+ channel blocker omega-conotoxin GVIA in conscious rabbits has previously been shown to result in a slowly developing hypotensive and sympatholytic effect, with peak changes observed after 48 h. The aim of the current study was to examine the distribution of [I-125]omega-conotoxin GVIA binding in rabbit brain alone or following a prior i.c.v. injection of omega-conotoxin GVIA to determine the site(s) of action of centrally administered omega-conotoxin GVIA. Brains were removed from rabbits 2 or 48 h after central administration of vehicle or non-labelled omega-conotoxin GVIA (30 pmol/kg, i.c.v.). Brain sections were then incubated with [I-125]omega-conotoxin GVIA (50 pM) and the density of specific [I-125]omega-conotoxin GVIA binding measured in dpm/mm(2) was determined by quantitative receptor autoradiography. In the vehicle group, highest densities of [I-125]omega-conotoxin GVIA binding sites (> 20 dpm/mm(2)) were detected in cortex, caudate, putamen, and the stratum oriens and stratum radiatum of the hippocampus. Prior (48 h) i.c.v. injection of omega-conotoxin GVIA resulted in a decrease in specific binding of [I-125]omega-conotoxin GVIA, particularly in cortex and some portions of the caudate and hippocampus. Lesser effects were observed with a prior (2 h) i.c.v, injection of omega-conotoxin GVIA. Central administration of omega-conotoxin GVIA may be acting to disrupt neurotransmission in higher brain regions which may, in turn, affect cardiovascular control mechanisms in the rabbit.