Early Responsiveness to Stimuli Paired With Different Stages Within the State of Alcohol Intoxication

Pautassi, Ricardo Marcos; Godoy, Juan Carlos; Spear, Norman E.; Molina, Juan Carlos

doi:10.1097/00000374-200205000-00008

Cited by 20 publications

(49 citation statements)

References 56 publications

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“…Infant and adults usually express conditioned aversions when stimuli are paired with ethanol (Pautassi et al, 2002). The expression of conditioned tactile preferences in prior studies has required prolonged pre-exposure to the pharmacological properties of EtOH (twenty days or more; Bienkowski et al, 1995;Reid et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…In turn, phase 2 was aimed at pairing the tactile CS with the initial, early ethanol postabsorptive interval, when blood ethanol concentrations are still rising. It has been suggested that during the onset of the state of intoxication ethanol may be exerting appetitive unconditional effects, while aversive effects are likely to emerge at later stages (Risinger & Cunningham, 1992;Pautassi et al, 2002). Hence, duration of phase 2 was meant to restrict conditioning to a temporal window where appetitive effects of the drug are more likely to be encountered.…”

Section: Second Conditioning Phasementioning

confidence: 99%

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Infant rats exhibit aversive learning mediated by ethanol's orosensory effects but are positively reinforced by ethanol's post-ingestive effects

Pautassi

Molina

Spear

2008

Pharmacology Biochemistry and Behavior

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Previous work suggests aversive and appetitive hedonic effects of intraorally delivered EtOH in preweanling rats. Pups are reluctant to perform an operant response when reinforced with intraoral EtOH infusions, a result suggesting aversive orosensory properties of EtOH. Yet, postabsorptive effects of ethanol seem capable of supporting appetitive conditioning. Two experiments were conducted to test this phenomenon. Both included a pre-exposure phase (postnatal day 13, PD13) comprising intraoral stimulation with water or EtOH. In Experiment 1, pups were given pairings between a tactile conditioned stimulus (CS) and intraoral infusions of EtOH or water. A subsequent tactile preference test revealed that pups spent significantly less on the EtOH-related CS relative to time spent on the alternative CS. In Experiment 2 pups were exposed to a texture CS (sandpaper) while intraorally infused with EtOH or during a later EtOH postinfusion interval. A tactile locational test conducted on PD16 indicated that EtOH-preexposed animals that experienced sandpaper paired with EtOH's postabsorptive effects exhibited a significant preference for the CS, even relative to a control group that experienced non-reinforced exposure to the tactile CS during conditioning. These results confirm that intraoral ethanol acts as an aversive tastant. A brief pre-exposure to EtOH allows later expression of appetitive learning mediated by the drug's postingestive effects.

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Section: Discussionmentioning

confidence: 99%

Section: Second Conditioning Phasementioning

confidence: 99%

Infant rats exhibit aversive learning mediated by ethanol's orosensory effects but are positively reinforced by ethanol's post-ingestive effects

Pautassi

Molina

Spear

2008

Pharmacology Biochemistry and Behavior

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“…This tub was kept at 34° C by means of a heating pad placed underneath. Following this initial isolation period subjects were implanted in their cheek with a polyethylene cannula (Pautassi et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, aversive effects of the drug are easily found by pairing a novel flavor or distinctive place with the post absorptive effects of EtOH. Animals will later exhibit strong taste or place avoidance, particularly when a high dose of EtOH is employed (Broadbent et al, 2002;Fidler et al, 2004;Pautassi et al, 2002). …”

Section: Introductionmentioning

confidence: 99%

Differential effects of ethanol and midazolam upon the devaluation of an aversive memory in infant rats

Pautassi

Nizhnikov

Molina

et al. 2007

Alcohol

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In infant rats, low doses of ethanol have been found to attenuate the aversive representation of an unconditioned stimulus (US) as assessed through a revaluation paradigm. This may be explained by early anxiolytic properties of EtOH. The present set of experiments was aimed at analyzing possible mechanisms of these putative anti-anxiety effects of EtOH. In a the first experiment, EtOH's effects upon the expression of citric acid-induced distress calls were compared with varying doses of midazolam (MDZ), a fast-acting GABA A agonist. Similar calming effects of 0.5 g/kg EtOH and 0.09 mg/kg MDZ were observed. Both drugs were then assessed in their capability to alter the expression of a conditioned aversion by devaluing the US. Aversive conditioning was conducted on postnatal day 14 (PD14) by pairing a lemon odor (conditioned stimulus, CS) with intraoral stimulation of citric acid (US). Control animals experienced both stimuli in an explicitly unrelated fashion. On PD 15 pups were briefly exposed to the citric acid solution under the effects of 0.5 g/kg EtOH, 0.09 mg/kg MDZ, or the respective vehicle for each drug. Pups were then tested in a two-way odor preference test (lemon vs. cineole). Both vehicle and MDZ-treated animals spent significantly less time near the lemon CS, thus expressing a citric-acid mediated odor aversion. This conditioned response was completely inhibited in pups that received 0.5 g/kg EtOH. Locomotor patterns at test were not affected by either EtOH or MDZ administration. A higher dose of MDZ (0.18 mg/kg, i.p) was also ineffective in attenuating the aversive memory. In summary, EtOH's devaluating capabilities are not shared by MDZ, indicating that these effects of EtOH may not be GABA-mediated. Appetitive motivational properties of EtOH or non-GABA A -mediated anti-anxiety effects (i.e, NMDA-related) could underlie this devaluation effect of ethanol.

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“…As with adult animals, high ethanol doses (1.2-3.0 g/kg yielding peak blood ethanol levels equivalent to 70-175 mg/100 ml, respectively) (84) act as aversive unconditioned stimuli in the infant rats, supporting the acquisition of chemosensory as well as tactile-conditioned aversions (65,(85)(86)(87)(88). Recently, it was reported that after pairing a surrogate nipple or a novel odor with low ethanol doses yielding 15-20 mg/100 ml blood ethanol levels, newborn rats (3-24 hrs old) increase their appetitive suckling activity in the presence of this nipple or odor; thus, this result indicated positive reinforcement from the ethanol (89-91).…”

Section: Learning About Ethanol In the Fetusmentioning

confidence: 99%

Fetal Learning About Ethanol and Later Ethanol Responsiveness: Evidence Against “Safe” Amounts of Prenatal Exposure

Abate

Pueta

Spear

et al. 2008

Exp Biol Med (Maywood)

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Near-term fetuses of different mammalian species, including humans, exhibit functional sensory and learning capabilities. The neurobiological literature indicates that the unborn organism processes sensory stimuli present in the amniotic fluid, retains this information for considerable amounts of time, and is also capable of associating such stimuli with biologically relevant events. This research has stimulated studies aimed at the analysis of fetal and neonatal learning about ethanol, a topic that constitutes the core of the present review. Ethanol has characteristic sensory (olfactory, taste, and trigeminal) attributes and can exert pharmacologic reinforcing effects. The studies under examination support the hypothesis that low to moderate levels of maternal ethanol intoxication during late pregnancy set the opportunity for fetal learning about ethanol. These levels of prenatal ethanol exposure do not generate evident morphologic or neurobehavioral alterations in the offspring, but they exert a significant impact upon later ethanol-seeking and intake behaviors. Supported by preclinical and clinical findings, this review contributes to strengthening the case for the ability of prenatal ethanol exposure to have effects on the postnatal organism. Keywords ethanol; fetal learning; associative conditioningThis review analyzes the impact of low to moderate prenatal levels of exposure to ethanol on later responding to ethanol and stimuli associated with ethanol. These levels of ethanol exposure might be viewed as "safe" but nevertheless have negative effects that might not be noticed for many years.We previously reviewed the literature, examining possible associations between early ontogenetic experiences with alcohol and subsequent affinity for ethanol ingestion and sensitivity to its reinforcing effects (postabsorptive consequences that increase behaviors aimed at obtaining ethanol or that generate preferences to stimuli signaling such consequences) (1). This review took into account fetal and infantile experiences involving acute or chronic exposure to ethanol and how they exerted significant effects upon subsequent ethanol 1To whom correspondence should be addressed at Instituto Ferreyra,

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Early Responsiveness to Stimuli Paired With Different Stages Within the State of Alcohol Intoxication

Cited by 20 publications

References 56 publications

Infant rats exhibit aversive learning mediated by ethanol's orosensory effects but are positively reinforced by ethanol's post-ingestive effects

Infant rats exhibit aversive learning mediated by ethanol's orosensory effects but are positively reinforced by ethanol's post-ingestive effects

Differential effects of ethanol and midazolam upon the devaluation of an aversive memory in infant rats

Fetal Learning About Ethanol and Later Ethanol Responsiveness: Evidence Against “Safe” Amounts of Prenatal Exposure

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