The mechanisms of resistance were investigated in a near isogenic perm
ethrin-resistant strain of Colorado potato beetle (Leptinotarsa deceml
ineata (Say)). The near isogenic strain was bred from a Massachusetts
field strain that was multiply resistant to a number of insecticides b
y backcrossing to a laboratory susceptible strain. Permethrin resistan
ce was principally associated with two contributing factors, an increa
sed level of carboxylesterase activity and a site insensitivity associ
ated with the nervous system. Pharmacokinetically, there were no diffe
rences noted in the rate of permethrin penetration or excretion betwee
n strains. An increased level of carboxylesterase activity was associa
ted with the permethrin-resistant strain resulting in a 1.5-fold great
er hydrolytic rate of a-naphthyl butyrate. Additionally, the permethri
n-resistant strain produced more hydrolytic metabolites of C-14-labele
d permethrin when incubated under in vivo and in vitro conditions comp
ared to the nearly isogenic susceptible strain. The increased carboxyl
esterase activity associated with permethrin resistance is largely mem
brane-associated when whole-body extracts are examined. Increased carb
oxylesterase activity showed a preference of alpha-naphthyl butyrate o
ver alpha-naphthyl acetate, suggestive of a more hydrophobic catalytic
center associated with the resistant form of enzyme activity. The nea
r isogenic permethrin-resistant strain was also determined to br cross
-resistant to DDT, indicating the possibility of site insensitivity as
an additional mechanism involved in permethrin resistance. Time to 50
% knockdown for the resistant strain was 3.6 times longer than for its
nearly isogenic susceptible strain (i.e., 56 min versus 15 min, respe
ctively). Recovery from permethrin-induced knockdown was largely attri
buted to enhanced oxidative metabolism of permethrin by the resistant
strain. Electrophysiological recordings determined the resistant strai
n to be recalcitrant to neuronal hyperexcitability caused by permethri
n in the susceptible strain. These findings are consistent with a nerv
e insensitivity factor associated with kdr and kdr-type resistances in
other insects. (C) 1995 Academic Press, Inc.