Blocking and Sensory Preconditioning Effects in Morphine Analgesic Tolerance: Support for a Pavlovian Conditioning Model of Drug Tolerance

Dafters, Richard; Hetherington, Marion M.; McCartney, Helen B.

doi:10.1080/14640748308400910

Cited by 38 publications

(18 citation statements)

References 15 publications

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“…The underlying assumption of many of these theories is that tolerance is the result of an endogenous compensatory system which functions to maintain homeostasis in the presence of drug effects or stimuli associated with the drug. Pavlovian rules of classical conditioning are thought to govern this process, and a plethora of data have been collected which support this idea (e.g., Adams et al 1969;Siegel 1976;Tiffany and Baker 1981;Dafters, et al 1983;Grisel, et al 1994).…”

Section: Introductionmentioning

confidence: 92%

Associative and non-associative mechanisms of morphine analgesic tolerance are neurochemically distinct in the rat spinal cord

1996

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Opiate tolerance involves both associative and non-associative changes. However, procedures designed to distinguish between these two processes have rarely been employed when investigating the physiological basis of such plasticity. The present experiments assessed some of the mechanisms contributing to both associative and non-associative decreases in morphine analgesic potency following repeated IV morphine administration (4 days, 5 mg/kg per day). For one group of rats, testing for morphine analgesia (tailflick) occurred in a context that had been repeatedly paired with morphine administration. Another group of rats, exposed equally to the testing context, handling procedures and morphine, was tested for morphine analgesia in a context that was specifically unpaired with prior drug. Although both of these groups showed a decrease in the drug effect following repeated administrations, those rats tested in the morphine-associated context were significantly more tolerant than the unpaired group. We evaluated the spinal cord involvement of NMDA receptors, as well as the peptide neurotensin in these two types of tolerance. NMDA receptors appeared to mediate non-associative changes in drug potency, as rats tested in either context were less tolerant when morphine administration was preceded with the non-competitive NMDA antagonist, MK-801 (2.5 and 5 nmol). Spinal neurotensin antagonism with [D-Trp11]neurotensin (3 pmol) selectively abolished associative tolerance. These findings provide information about the mechanisms of opiate tolerance and support the distinction between associative and non-associative processes underlying these changes.

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Section: Introductionmentioning

confidence: 92%

Associative and non-associative mechanisms of morphine analgesic tolerance are neurochemically distinct in the rat spinal cord

1996

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“…Further experiments have shown that tolerance to the analgesic effect of morphine is also subject to blocking (Dafters et al, 1983) and overshadowing (Walter & Riccio, 1983), the better known forms of competition between CSs.…”

Section: Audiovisual and Contextual Cues Morphine And Conditionementioning

confidence: 99%

Classical conditioning and pain: Conditioned analgesia and hyperalgesia

2014

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This article reviews situations in which stimuli produce an increase or a decrease in nociceptive responses through basic associative processes and provides an associative account of such changes. Specifically, the literature suggests that cues associated with stress can produce conditioned analgesia or conditioned hyperalgesia, depending on the properties of the conditioned stimulus (e.g., contextual cues and audiovisual cues vs. gustatory and olfactory cues, respectively) and the proprieties of the unconditioned stimulus (e.g., appetitive, aversive, or analgesic, respectively). When such cues are associated with reducers of exogenous pain (e.g., opiates), they typically increase sensitivity to pain. Overall, the evidence concerning conditioned stress-induced analgesia, conditioned hyperalagesia, conditioned tolerance to morphine, and conditioned reduction of morphine analgesia suggests that selective associations between stimuli underlie changes in pain sensitivity.

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“…Los estímulos condicionados a la droga se ven influidos, por ejemplo, por procedimientos de extinción (Crombag y Shaham, 2002;MacRae y Siegel, 1997), renovación (Betancourt, Corada, et al, 2008), inhibición externa (Siegel, Baptista, Kim, McDonald y Weise-Kelly, 2000;, preexposición al EC (Goodinson y Siegel, 1995), modulación (Betancourt, Inostroza et al, 2008;Ramos et al, 2002), ensombrecimiento (Walter y Riccio, 1983), bloqueo (Dafters, Hetherington, y McCartney, 1983), competencia de claves interoceptivas y exteroceptivas (Betancourt, Díaz y Quezada, 2008), y transferencia Pavlovianas-instrumentales (Quezada, Alarcón, Miguez y Betancourt, 2009), entre otros.…”

Section: Introductionunclassified

Reinstauración de la tolerancia al etanol: la función del contexto

2013

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Marion Inostroza por su colaboración en la ejecución del experimento.Contacto: G. Miguez, State University of New York at Binghamton, Binghamton, NY, 13902-6000, United States of America. gmiguez1@binghamton.edu ResumenEn esta investigación se estudió la reinstauración de la tolerancia al efecto atáxico del etanol en tres grupos de ratas. Para todos los sujetos un estímulo visual (i.e., estímulo condicionado; EC) fue pareado en repetidas ocasiones con el efecto de una dosis de etanol (i.e., estímulo incondicionado, EI). Luego, los sujetos recibieron ensayos no pareados del EC con el fin de extinguir la asociación EC-EI formada en la fase previa. Posterior a la extinción, un grupo recibió una presentación no pareada del EI en el contexto de extinción, un segundo grupo recibió una presentación no pareada del EI en un contexto novedoso, y el tercer grupo no recibió presentaciones del EI. Finalmente, se evaluó la respuesta de tolerancia al efecto atáxico del etanol en ensayos de readquisición. Los datos obtenidos demuestran que la administración no señalada del efecto del etanol en el organismo reinstaura la respuesta de tolerancia anteriormente extinguida, y que el contexto donde se realiza la administración influye en la magnitud de la reinstauración de la respuesta condicionada de tolerancia. Estos datos, juntos con otros de experimentos previos, arrojan luces sobre los mecanismos que producen recaídas en terapias de exposición a claves.Palabras clave: alcohol, adicción, condicionamiento Pavloviano, tolerancia a las drogas, reinstauración. AbstractThe reinstatement of the ataxic effect of ethanol was studied in three groups of rats. All subjects received a visual stimulus (i.e., conditioned stimulus, CS), paired in repeated occasions with the effect of an ethanol dose (i.e., unconditioned stimulus, US). Then, all subjects received unpaired presentations of the CS aimed at extinguishing the CS-US association formed in the previous phase. After extinction, one group received an unpaired presentation of the US in the extinction context, a second group received an unpaired presentation of the US in a new context, and a third group did not receive US presentations. Finally, the tolerance response to the ataxic effect of ethanol was assessed in reacquisition trials. The results show that a nonsignaled administration of ethanol is efficient in reinstating an extinguished tolerance response, and that the context in which the ethanol is administered determines the magnitude of the reinstated conditioned response. This study, together with previous data, helps to understand the mechanisms of relapse in cue exposure therapies.

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Blocking and Sensory Preconditioning Effects in Morphine Analgesic Tolerance: Support for a Pavlovian Conditioning Model of Drug Tolerance

Cited by 38 publications

References 15 publications

Associative and non-associative mechanisms of morphine analgesic tolerance are neurochemically distinct in the rat spinal cord

Associative and non-associative mechanisms of morphine analgesic tolerance are neurochemically distinct in the rat spinal cord

Classical conditioning and pain: Conditioned analgesia and hyperalgesia

Reinstauración de la tolerancia al etanol: la función del contexto

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