Las propiedades de refuerzo central del etanol están mediadas por sistemas de opiáceos endógenos: efectos de los antagonistas de los opiáceos Mu y Kappa

Contenido principal del artículo

Michael E. Nizhnikov
Elena I. Varlinskaya
Norman E. Spear

Resumen

Los sistemas de opiáceos endógenos están implicados en los efectos reforzantes del alcohol y pueden desempeñar un papel sustancial en modular los efectos reforzantes centrales del etanol en la temprana ontogenia. El presente estudio indagó esta posibilidad a través de un paradigma de condicionamiento olfatorio en el que la administración central de etanol sirvió como estímulo incondicionado (EI). En el experimento 1, los neonatos de rata fueron pre-tratados con antagonistas selectivos para los receptores mu o kappa (CTOP y nor-BNI, respectivamente) y luego entrenados en condicionamiento olfatorio. El experimento 2 evaluó la capacidad de un antagonista kappa de corta duración (GNTI) en alterar la capacidad reforzante del etanol. El experimento 3 investigó si el bloqueo farmacológico de los receptores opiáceos podía causar una alteración inespecífica del condicionamiento olfatorio. Para ello se empleó como EI la administración intraoral de quinina. La administración central de los antagonistas opiáceos mu y kappa bloqueó los efectos reforzantes del etanol. La efectividad de GNTI fue similar a nor-BNI. Es poco probable que los efectos de antagonistas opiáceos sobre el reforzamiento al etanol sean explicados por una disrupción general de todos los tipos de condicionamiento; desde el momento en que CTOP no afecto el reforzamiento aversivo inducido por la infusión intraoral de quinina. Estos resultados respaldan la hipótesis de que las propiedades reforzantes del etanol en el neonato de rata están mediadas por la actividad endógena de los receptores opiáceos mu y kappa.

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Las propiedades de refuerzo central del etanol están mediadas por sistemas de opiáceos endógenos: efectos de los antagonistas de los opiáceos Mu y Kappa. (2009). Revista Argentina De Ciencias Del Comportamiento, 1(1), 1-12. https://doi.org/10.32348/1852.4206.v1.n1.5299
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Las propiedades de refuerzo central del etanol están mediadas por sistemas de opiáceos endógenos: efectos de los antagonistas de los opiáceos Mu y Kappa. (2009). Revista Argentina De Ciencias Del Comportamiento, 1(1), 1-12. https://doi.org/10.32348/1852.4206.v1.n1.5299

Referencias

Aloyo VJ, Romano AG, & Harvey JA (1993). Evidence for an involvement of the µ-type of opioid receptor in the modulation of learning. Neuroscience, 55, 511-519.

Aragon, C. M., and Amit, Z. (1992). The effect of 3-amino1,2,4-triazole on voluntary ethanol consumption: Evidence for catalse involvement in the mechanism of action. Neuropharmacology. 31, 709-712.

Bals-Kubik R, Ableitner A, Herz A, & Shippenberg TS (1993). Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. J Pharmacol Exp Ther., 264, 489-495.

Bals-Kubik R, Herz A, & Shippenberg TS (1989). Evidence that the aversive effects of opioid antagonists and kappa-agonists are centrally mediated. Psychopharmacology, 98, 203-206.

Barr GA, Wang S & Carden, S (1994). Aversive properties of the k opioid agonist U50,488 in the week-old rat pup. Psychophamacology, 113, 422-428.

Bechara A, & Van der Kooy D, (1987). Kappa receptors mediate the peripheral aversive effects of opiates. Pharmacol Biochem Behav., 28, 227-233.

Boyadjieva NI, Sarkar DK (1997). Effects of ethanol on basal and prostaglandin E1-induced increases in betaendorphin release and intracellular camp levels in hypothalamic cells. Alcohol Clin Exp Res, 21, 1005-1009.

Broadbear JH, Negus SS, Butelman ER, de Costa BR, Woods JH (1994). Differential effects of systemically administered nor-binal-trophimine (nor-BNI) on Kopioid agonists in the mouse writing assay. Psychopharmacology, 115, 311-319.

Cerro SD & Borrell J (1990). Dynorphin 1-17 can enhance or impair retention of an inhibitory avoidance response in rats. Life Sci., 47, 1453-1462.

Chavkin C, James IF, Goldstein A (1982). Dynorphin is a specific endogenous ligand of the ? opioid receptor. Science, 215, 413-415.

Cheslock SJ, Varlinskaya EI, Petrov ES, Silveri MM, Spear LP, Spear NE (2001). Ethanol as a reinforcer in the newborn’s first suckling experience. Alcohol Clin Exp Res., 25, 391-402.

Cheslock SJ, Varlinskaya EI, Petrov ES, Spear NE (2000). Rapid and robust olfactory conditioning with milk before suckling experience: promotion of nipple attachment in the newborn rat. Behav Neurosci, 114, 484-495.

Cheslock SJ, Sanders SK, & Spear NE (2004). Learning during the newborn’s first meal: special resistance to retroactive interference. Dev Sci., 7, 581- 598.

Cicala GA, Azorlosa JL, Estall LB, & Grant SJ (1990). Endogenous opioids interfere with Pavlovian secondorder fear conditioning. Psychological Science, 1, 312-315.

Davidson D & Amit Z (1997). Naltrexone blocks acquisition of voluntary ethanol in take in rats. Alcohol Clin Exp Res., 21, 677-683.

De Waele JP, Gianoulakis C (1993) Effect of single and repeated exposure to ethanol on the hypothalamic ßendorphin release by the C57BL/6 and DBA/2 strains of mice. Neuroendocrinology, 57, 700-709.

De Waele JP, Papachristou ND, Gianoulakis C (1992) The alcohol-preferring C57BL/6 mice present an enhanced sensitivity of the hypothalamic ß-endorphin system to ethanol than the alcohol-avoiding mice. J Pharmacol Exp Ther, 261, 788-794.

DeWitte P (1984). Naloxone reduces alcohol intake in a free choice procedure even when both drinking bottles contain saccharin sodium or quinine substances. Neuropsychobiology, 12, 73-77.

Eilam D & Smotherman WP (1998). How the neonatal rat gets to the nipple: common motor modules and their involvement in the expression of early motor behavior. Dev Psychobio, 32, 57-66.

Endoh T, Matsuura H, Tanaka C, Nagase H (1992). Norbinaltrophimine: a potent and selective kappa-opioid receptor antagonist with long-lasting activity in vivo. Arch Int Pharmacodyn Ther., 316, 30-42.

Fadda P, Tronci S, Colombo G, Fratta W (1999) Differences in the opioid system in selected brain regions on alcohol-preferring and alcohol-nonpreferring rats. Alcohol Clin Exp Res., 23, 1296-1305.

Fanselow MS, Calcagnetti DJ & Helmstetter FJ (1989). Modulation of appetitively and aversively motivated behavior by the kappa opioid antagonist MR2266. Beh. Neuro., 103, 663-672.

Froehlich JC (1993). Interactions between alcohol and the endogenous opioid system. In Zakhari, S. (Ed.), Alcohol and the endocrine system (pp. 31-35). NIAAA Research Monograph 23, Bethesda, MD.

Froehlich JC, Harts J, Lumeng L & Li TK (1990). Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference. Pharmacol Biochem Behav., 35, 385-390.

Gatto GJ, McBride WJ, Murphy JM, Lumeng L & Li TK (1994). "Ethanol self-infusion into the ventral tegmental area by alcohol-preferring rats." Alcohol, 11, 557-564.

Gianoulakis C (1996). Implications of endogenous opioids and dopamine in alcoholism: Human and basic science studies. Alcohol Alcohol., 31, 33-42.

Hernandez LL & Powell DA (1983). Naloxone induces multiple effects on aversive Pavlovian conditioning in rabbits. Behav Neurosci., 97, 478-491.

Herz A (1997). Endogenous opioid systems and alcohol addiction. Psychopharmacology, 129, 99-111.

Holson RR, Pearce B (1992). Principals and pitfalls in the analysis of prenatal treatment effects in multiparous species. Neurotoxicol Teratol, 14, 221-228.

Hubbell CL, Czirr SA, Hunter GA, Beaman CM, LeCann NC & Reid LD (1986). Consumption of ethanol solution is potentiated by morphine and attenuated by naloxone persistently across repeated daily administration. Alcohol, 3, 39-54.

Hyytiä P, Kiianmaa K (2001). Suppression of ethanol responding by centrally administered CTOP and naltrindole in AA and Wistar rats. Alcohol Clin Exp Res, 25, 33.

Hyytia P (1993). Involvement of mu opioid receptors in alcohol drinking by alcohol-preferring AA rats. Pharmacol Biochem Behav., 45, 697-701.

Jamensky NT, Gianoulakis C (1997). Content of dynorphins and kappa-opioid receptors in distinct brain regions of C57BL/6 and DBA/2 mice. Alcohol Clin Exp Res., 21, 1455-1464.

Jewett DC, Cleary J, Levine AS, Schaal DW, Thompson T (1995). Effects of neuropeptide Y, insuline, 2- deoxyglucose, and food deprivation on food-motivated behavior. Psychopharmacology, 120, 267-271.

Jewett DC, Grace MK, Jones RM, Billington CJ, Portoghese PS, Levine AS (2001). The kappa-opioid antagonist GNTI reduces U50,488-, DAMGO-, and deprivationinduced feeding, but not butorphanol- and neuropeptide Y-induced feeding in rats. Brain Res., 909, 75-80.

Jewette DC, Grace M, Billington CJ, Levine AS (1997). Duration of the anorectic action of norbinaltrophimine on neuropeptide-Y induced feeding in rats. Soc. Neurosci. Abstr., 23, 1346.

Krishnan-Sarin S, Jing SL, Kurtz DL, Zweifel M, Portoghese PS, Li TK & Froehlich JC (1995a). The delta opioid receptor antagonist naltrindole attenuates both alcohol and saccharin intake in rats selectively bred for alcohol preference. Psychopharmacology, 120, 177-185.

Krishnan-Sarin S, Portoghese PS, Li TK, & Froehlich JC (1995b). The delta2-opioid receptor antagonist naltriben selectively attenuates alcohol intake in rats bred for alcohol preference. Pharmacol Biochem Behav., 52, 153-159.

Kuzmin A, Sandin J, Terenius L & Ogren SO (2003). Acquisition, expression, and reinstatement of ethanolinduced conditioned place preference in mice: Effects of opioid receptor-like 1 receptor agonists and naloxone. J Pharmacol Exp Ther. 304, 310-318.

Lindholm S, Werme M, Brene S, Franck J (2001) The selective kappa-opioid receptor agonist U50,488H attenuates voluntary ethanol intake in the rat. Behav Brain Res., 120, 137-146.

Marfaing-Jallat P, Miceli C, LeMegnen J (1983) Decrease in ethanol consumption by naloxone in naive and dependent rats. Pharmacol Biochem Behav 18, 537-539.

Matsuzawa S, Suzuki T, Misawa M, Nagase H (1999) Different roles of µ, ?- and ?-opioid receptors in ethanol-associated place preference in rats exposed to conditioned fear stress. Europ J Pharmacol 368, 9-16.

Matsuzawa S, Suzuki T, & Misawa M (2000). Involvement of mu-opioid receptor in the salsolinol-associated place preference in rats exposed to conditioned fear stress. Alcohol Clin Exp Res., 24, 366-372.

Matsuzawa S, Suzuki T, Misawa M, & Nagase H (1998). Involvement of mu- and delta-opioid receptors in the ethanol-associated place preference in rats exposed to foot shock stress. Brain Res., 803, 169-177.

Mitchell JM, Liang MT, Fields HL (2005) A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats. Psychopharmacology 182, 384-392.

Mori T, Nomura M, Yoshizawa K, Nagase H, Narita M, & Suzuki T (2004). Differential properties between TRK820 and U-50,488H on the discriminative stimulus effects in rats. Life Scie., 75, 2473-2482.

Mucha RF & Herz A (1985). Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology, 86, 274-280.

National Institutes of Health (1986). Guide for the Care and Use of Laboratory Animals (DHEW Publication No. 86-23). US Government Printing Office, Washington, DC.

Nestby P, Schoffelmeer ANM, Homberg JR, Wardeh G, De Vries TJ, Mulder AH, Vanderschuren LJMJ (1999). Bremazocine reduces unrestricted free-choice ethanol self-administration in rats without affecting sucrose preference. Psychopharmacology 142, 309-317.

Nizhnikov ME, Varlinskaya, EI, Petrov, ES, and Spear, NE (2006). Reinforcing properties of ethanol in neonatal rats: Involvement of the opioid system. Behav. Neurosci. 120, 267-280.

Nizhnikov, M.E., Petrov, E.S., Varlinskaya, E.I., & Spear, N.E. (2002). Newborn first suckling experience: Taste differentiation and suckling plasticity. Physiol Behav., 76, 181-198.

Nizhnikov, M.E., Petrov, E.S. & Spear, N.E. (2002). Olfactory aversive conditioning in the newborn (3-hrold) rat impairs later suckling for water and milk. J Exp Psychol Anim Behav Process., 28, 277-283.

Nizhnikov, M.E., Molina, J.C., & Spear, N.E. (2007). Central reinforcing effects of ethanol are blocked by catalase inhibition. Alcohol, 41, 525-534.

Olive MF, Koenig NH, Nannini MA, Hodge CW (2001). Stimulation of endorphin neurotransmission in the nucleus accumbens by ethanol, cocaine and amphetamine. J Neurosci 21, RC184 (1-5).

Pautassi RM, Godoy JC, Spear NE, Molina JC (2002). Early responsiveness to stimuli paired with different stages within the state of alcohol intoxication. Alcohol Clin Exp Res., 26, 644-654.

Pellis SM, Pellis VC, & Teitelbaum P (1991). Air righting without the cervical righting reflex in adult rats. Beh Brain Res., 45, 185-188.

Petrov ES, Nizhnikov ME, Varlinskaya EI, Spear NE (2006) Dynorphin A (1–13) and responsiveness of the newborn rat to a surrogate nipple: Immediate behavioral consequences and reinforcement effects in conditioning. Beh Brain Res., 170, 1-14.

Petrov ES, Varlinskaya EI, Spear NE (2001) Selfadministration of ethanol and saccharin in newborn rats: Effects on suckling plasticity. Behav Neurosci 115, 1318-1331.

Petrov ES, Varlinskaya EI, & Smotherman WP (1997). The newborn rat ingests fluids through a surrogate nipple: a new technique for the study of early suckling behavior. Physiol Behav., 62, 1155-1158.

Petrov ES, Varlinskaya EI & Smotherman WP (1998). Endogenous opioids in the first suckling episode in the rat. Dev Psychobiol., 33, 175-183.

Picker MJ, Methewson C, Allen RM (1996). Opioids and rate of positively reinforced behavior. III. Antagonism by the long-lasting kappa antagonist norbinaltrophimine. Behav. Pharmacol. 7, 495-504.

Quertemont, E., Escarabajal, M.D., and De Witt, P. (2003). Role of catalase in ethanol-induced conditioned taste aversion: A study with 3-amino-1,2,4-triazole. Drug. Alcohol. Depend. 70, 77-83.

Rasmussen DD, Bryant CA, Boldt BM, Colasurdo EA, Levin N, Wilkinson CW (1998). Acute alcohol effects on opiomelanocortinergic regulation. Alcohol Clin Exp Res 22, 789-801.

Rodd ZA, Bell RL, Melendez RI, Kuc KA, Lumeng L, Li TK, Murphy JM & McBride WJ (2004b). Comparison of intracranial self-administration of ethanol within the posterior ventral tegmental area between alcoholpreferring and Wistar rats. Alcohol Clin Exp Res., 28, 1212-1219.

Rodd ZA, McKinzie DL, Crile RS, Murphy JM & McBride WJ (2000). Regional heterogeneity for the intracranial self-administration of ethanol within the ventral tegmental area of female Wistar rats. Psychopharmacology 149, 217-224.

Rodd ZA, Melendez RI, Bell RL, Kuc KA, Zhang Y, Murphy JM & McBride WJ (2004a). Intracranial selfadministration of ethanol within the ventral tegmental area of male wistar rats: Evidence for involvement of dopamine neurons. The J of Neurosci., 24, 1050-2057.

Sandi C, Borrell J, Guaza C (1988). Kappa-opioid receptors and relapse-like drinking in long-term ethanolexperienced rats. Psychopharmacology, 153, 93-102.

Schulteis G & Martinez Jr JL (1990). ICI 174,864, a selective delta opioid antagonist, reverses the learning impairment produced by [leu]enkephalin. Psychopharmacology, 100, 102-109.

Shippenberg TS & Herz A (1986). Differential effects of mu and kappa opioid systems on motivational processes. NIDA research monograph, 75, 563-566.

Shippenberg TS & Herz A (1987). Motivational properties of opioids. Pol. J. Pharmacol. Pharm., 39, 577-583.

Smotherman WP, Petrov ES, Varlinskaya EI (1997) Experimental study of the first suckling episode: Rat pups ingest fluids through the surrogate nipple. Behav Neurosci 111, 1383-1394.

Ulm RR, Volpicelli JR & Volpicelli LA (1995). Opiates and alcohol self-administration in animals. J. Clin. Psychiatry, 56, 5-14.

Varlinskaya EI, Petrov ES, Cheslock SJ, Spear NE (1999). A new model of ethanol self-administration in newborn rats: Gender effects on ethanol ingestion through a surrogate nipple. Alcohol Clin Exp Res 23, 1368-1376.

Varlinskaya, E. I., Petrov, E. S., & Smotherman, W. P. (1996). Classical conditioning in the fetal rat: Reinforcing properties of dynorphin A (1-13). Behav Neurosci., 110, 154-167.

Westbrook RF, Greeley JD, Nabke CP, & Swinbourne AL (1991). Aversive conditioning in the rat: Effects of a benzodiazepine and of an opioid agonist and antagonist on conditioned hypoalgesia and fear. J of Experi Psych., 17, 219-230.

Wettstein JG, Grouhel A. (1996). Opioid antagonist profile of SC nor-binaltorphimine in the formalin paw assay. Pharmacol. Biochem. Behav. 53, 411-6.