R. Spanagel et al., ENDOGENOUS K-OPIOID SYSTEMS IN OPIATE WITHDRAWAL - ROLE IN AVERSION AND ACCOMPANYING CHANGES IN MESOLIMBIC DOPAMINE RELEASE, Psychopharmacology, 115(1-2), 1994, pp. 121-127
The kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) was
recently shown to potentiate certain overt withdrawal signs in morphi
ne-dependent rats. The present study sought to further assess this phe
nomenon by examining the influence of nor-BNI treatment upon the condi
tioned place aversion associated with the naloxone-precipitated withdr
awal syndrome. In addition, in vivo microdialysis studies were conduct
ed in morphine-dependent rats to determine whether nor-BNI treatment c
an modify withdrawal-induced changes in basal dopamine (DA) release wi
thin the mesolimbic system. Rats were pretreated with either saline or
a single dose of nor-BNI and then received ascending doses of morphin
e for 10 days. A withdrawal syndrome was then precipitated by the admi
nistration of naloxone (1 mg/kg SC). In rats which received chronic mo
rphine injections, administration of naloxone produced a characteristi
c withdrawal syndrome and a marked aversion for an environment previou
sly associated with naloxone-precipitated withdrawal. Nor-BNI treatmen
t potentiated most overt signs of physical dependence. This treatment
also resulted in a greater withdrawal-induced place aversion. Morphine
-dependent rats exhibited a marked reduction in basal mesolimbic DA re
lease. An even greater decrease in basal DA release was observed in no
r-BNI treated rats. These results suggest that endogenous kappa-system
s are important in the modulation of mesolimbic DA release and the acc
ompanying place aversion which occurs during opiate withdrawal.