INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A role for KOR in ethanol-induced aversion?
Autor/es:
PAUTASSI RM
Lugar:
Sapporo
Reunión:
Congreso; 2012 International Society for Biomedical Research on Alcoholism (ISBRA) World Congress; 2012
Institución organizadora:
Science Council of Japan
Resumen:
The motivational effects of ethanol result from the interaction of ethanol?s appetitive
and aversive effects. Substantial data indicates that the appetitive effects of ethanol are
modulated by μ and δ opioid receptors. For instance, conditioned place preference by
ethanol is blocked by general (e.g., naloxone) and specific µ and δ opioid antagonists.
Less is known, however, about the central mechanisms underlying the aversive effects
of ethanol. Intracerebral administration of ethanol facilitates the release of dynorphin, the
endogenous ligand of kappa opioid receptors (KOR), which is involved in the mediation
of dysphoria and other aversive effects. Kappa antagonists have been observed to reduce
some aversive effects of ethanol (e.g., hypothermia). In the present study we assessed the
role of KOR in a second-order schedule of ethanol-induced conditioned place preference
and in ethanol-induced motor activation. Both paradigms are considered to measure
the appetitive effects of ethanol. The hypothesis was that ethanol-induced aversion
is partially mediated by KOR activation. Therefore, we expected kappa agonism and
antagonism to block and promote ethanol?s appetitive effects, respectively. Consistent
with previous reports, prolonged spiradoline (U62,066E)-induced activation of the KOR
system promoted the emergence of ethanol-induced appetitive reinforcement. This result
probably reflects negative reinforcing (i.e., anxiolytic) effects of ethanol. Administration
of U62,066E just before conditioning tended to decrease ethanol-induced CPP, although
the effect was not statistically significantly. KOR agonism did block, however, ethanol-
induced motor stimulation during the rising limb of the blood ethanol curve. Perhaps
more important, high-dose ethanol (2.0 g/kg) induced appetitive reinforcement only in
rats injected with the KOR antagonist kappa 5?-guanidinylnaltrindole dihydrochloride
(GNTI) before conditioning. The results underscore the role of the KOR system in ethanol
reinforcement and support the hypothesis that KOR antagonism can result in lessened
expression of ethanol?s aversive effects and, therefore, greater expression of ethanol?s
appetitive effects. Acknowledgements: Grants PIP CONICET 2010-2012 and PICT-PRH3
(Argentina) and support from SUNY Res. Foundation.