Jb. Bedingfield et al., Peripheral opioid receptors may mediate a portion of the aversive and depressant effect of EtOH: CPP and locomotor activity, ALCOHOL, 18(2-3), 1999, pp. 93-101
Previous investigators have reported that peripheral opioid receptors (loca
ted in the gut) may produce aversive effects when activated. Opioid recepto
rs can be activated by endogenous opioids or by-products of ethanol (EtOH)
metabolism [e.g., tetrahydroisoquinolines (TIQs)]; both are stimulated foll
owing EtOH consumption. Therefore, we tested the hypothesis that a portion
of the aversive or depressant effects of EtOH may be mediated through, or m
odulated by, peripheral opioid receptors. Conditioned place preference (CPP
) and locomotor activity were the dependent variables. Prior to EtOH gavage
, we antagonized the peripheral opioid receptors with methylnaltrexone (MNT
X), an opioid antagonist that does not easily pass through the blood-brain
barrier. The effects of EtOH were found to be dose dependent: 1.5 g/kg was
hedonically neutral but depressed locomotor activity; 2.25 g/kg EtOH was av
ersive and also depressed locomotor activity. MNTX (32 mg/kg) treatment was
rewarding and stimulated motor activity (especially during the first condi
tioning session). When combined, 1.5 g/kg EtOH tended to enhance the reward
ing effects of MNTX whereas MNTX blocked the aversive effects of 2.25 g/kg
EtOH. During, the first conditioning session EtOH attenuated the motor stim
ulant effects of MNTX whereas MNTX antagonized the motor depressant effects
of EtOH; there was little effect of MNTX on EtOH-induced motor depression
during subsequent conditioning sessions. Pretreatment with various doses of
MNTX (0.1, 1.0, 10.0, 32.0 mg/kg) of rats receiving 1.5 g/kg EtOH indicate
d the effects of MNTX were dose dependent. Drug-induced locomotor activity
and time spent in the conditioned compartment were positively correlated, s
uggesting that both behaviors were homologous. The data suggest that periph
eral opioid receptors participate in mediating or modulating a portion of t
he behavioral effects of EtOH. (C) 1999 Elsevier Science Inc. All rights re
served.