Naloxone attenuation of ethanol-reinforced operant responding in infant rats in a re-exposure paradigm

Miranda-Morales, Roberto Sebastián; Molina, Juan Carlos; Spear, Norman E.; Abate, Paula

doi:10.1007/s00213-011-2402-5

Cited by 19 publications

(33 citation statements)

References 61 publications

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“…Therefore, data were collapsed across sex for all the remaining analyses. The absence of sex effects has also been observed in prior studies when employing a variety of reinforcers in operant conditioning tasks during early ontogeny (Bordner et al, 2008; March et al, 2009; Miranda-Morales et al, 2010, 2012a,b, 2014). …”

Section: Methodssupporting

confidence: 57%

Brain Acetaldehyde Exposure Impacts upon Neonatal Respiratory Plasticity and Ethanol-Related Learning in Rodents

Acevedo

D'aloisio

Haymal

et al. 2017

Front. Behav. Neurosci.

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Prior studies indicate that neonates are very sensitive to ethanol's positive reinforcing effects and to its depressant effects upon breathing. Acetaldehyde (ACD) appears to play a major role in terms of modulating early reinforcing effects of the drug. Yet, there is no pre-existing literature relative to the incidence of this metabolite upon respiratory plasticity. The present study analyzed physiological and behavioral effects of early central administrations of ethanol, acetaldehyde or vehicle. Respiration rates (breaths/min) were registered at post-natal days (PDs) 2 and 4 (post-administration time: 5, 60, or 120 min). At PD5, all pups were placed in a context (plethysmograph) where they had previously experienced the effects of central administrations and breathing patterns were recorded. Following this test, pups were evaluated using and operant conditioning procedure where ethanol or saccharin served as positive reinforcers. Body temperatures were also registered prior to drug administrations as well as at the beginning and the end of each specific evaluation. Across days, breathing responses were high at the beginning of the evaluation session and progressively declined as a function of the passage of time. At PDs 2 and 4, shortly after central administration (5 min), ACD exerted a significant depression upon respiration frequencies. At PD5, non-intoxicated pups with a prior history of ACD central administrations, exhibited a marked increase in respiratory frequencies; a result that probably indicates a conditioned compensatory response. When operant testing procedures were conducted, prior ethanol or ACD central administrations were found to reduce the reinforcing effects of ethanol. This was not the case when saccharin was employed as a reinforcer. As a whole, the results indicate a significant role of central ACD upon respiratory plasticity of the neonate and upon ethanol's reinforcing effects; phenomena that affect the physiological integrity of the immature organism and its subsequent affinity for ethanol operationalized through self-administration procedures.

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Section: Methodssupporting

confidence: 57%

Brain Acetaldehyde Exposure Impacts upon Neonatal Respiratory Plasticity and Ethanol-Related Learning in Rodents

Acevedo

D'aloisio

Haymal

et al. 2017

Front. Behav. Neurosci.

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“…In the preclinical literature the use of operant techniques to evaluate the motivational effects of ethanol during early ontogeny has been recently documented in the literature (Bordner, Molina, & Spear, 2008; March, Abate, Spear, & Molina, 2009; Miranda-Morales, Molina, Spear, & Abate, 2010, 2012a; Miranda-Morales, Spear, Nizhnikov, Molina, & Abate, 2012b; Ponce, Pautassi, Spear, & Molina, 2008). In 1-day-old rats, ethanol's sensorial properties were sufficient to promote vigorous operant responses when ethanol ingestion was contingent upon operant behavior.…”

Section: Introductionmentioning

confidence: 99%

“…Other studies showed that this sensitivity to ethanol reinforcement during early ontogeny can also be observed during the second postnatal week of the infant rat. For instance, self-administration of ethanol was established in terms of operant responding in preweanling rats with no previous exposure to the drug (Miranda-Morales, Molina, et al, 2012a; Miranda-Morales, Spear, et al, 2012b; Ponce et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats

Miranda-Morales

Nizhnikov

Spear

2014

Alcohol

Self Cite

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Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17–20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development.

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“…Therefore, data were collapsed across sex for all of the subsequent analyses. The lack of sex effects was not unexpected: previous studies working with ethanol-related effects in rats of the present age (Arias & Chotro, 2005; Chotro & Arias, 2003; Miranda-Morales, Molina, et al, 2012; Miranda-Morales, Spear, et al, 2012) usually have found no significant effects of gender or interaction with other factors.…”

Section: General Methodsmentioning

confidence: 52%

“…On PD 13, infants were separated from their dams, cannulated, and placed in pairs in a holding cage (45 × 20 × 20 cm). Intraoral cannulation was performed using a procedure extensively described in previous studies (Chotro & Arias, 2003; Miranda-Morales, Molina, Spear, & Abate, 2012; Miranda-Morales, Spear, Nizhnikov, Molina, & Abate, 2012; Spear, Specht, Kirstein, & Kuhn, 1989). The entire procedure took less than 5 sec per pup.…”

Section: General Methodsmentioning

confidence: 99%

New evidence of ethanol's anxiolytic properties in the infant rat

Miranda-Morales

Nizhnikov

Waters

et al. 2014

Alcohol

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Ethanol induces appetitive, aversive, and anxiolytic effects that are involved in the development of ethanol use and dependence. Because early ethanol exposure produces later increased responsiveness to ethanol, considerable effort has been devoted to analysis of ethanol's appetitive and aversive properties during early ontogeny. Yet, there is a relative scarcity of research related to the anxiolytic effects of ethanol during early infancy, perhaps explained by a lack of age-appropriate tests. The main aim of this study was to validate a model for the assessment of ethanol's anxiolytic effects in the infant rat (postnatal days 13– 16). The potentially anxiolytic effects of ethanol tested included: i) amelioration of conditioned place aversion, ii) ethanol intake in the presence of an aversive conditioned stimulus, iii) the inhibitory behavioral effect in an anxiogenic environment, and iv) innate aversion to a brightly illuminated area in a modified light/dark paradigm. Ethanol doses employed across experiments were 0.0, 0.5, and 2.0 g/kg. Results indicated that a low ethanol dose (0.5 g/kg) was effective in attenuating expression of a conditioned aversion. Ethanol intake, however, was unaffected by simultaneous exposure to an aversive stimulus. An anxiogenic environment diminished ethanol-induced locomotor stimulation. Finally, animals given 0.5 g/kg ethanol and evaluated in a light/dark box showed increased time spent in the illuminated area and increased latency to escape from the brightly lit compartment than rats treated with a higher dose of ethanol or vehicle. These new results suggest that ethanol doses as low as 0.5 g/kg are effective in ameliorating an aversive and/or anxiogenic state in preweanling rats. These behavioral preparations can be used to assess ethanol's anxiolytic properties during early development.

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Naloxone attenuation of ethanol-reinforced operant responding in infant rats in a re-exposure paradigm

Cited by 19 publications

References 61 publications

Brain Acetaldehyde Exposure Impacts upon Neonatal Respiratory Plasticity and Ethanol-Related Learning in Rodents

Brain Acetaldehyde Exposure Impacts upon Neonatal Respiratory Plasticity and Ethanol-Related Learning in Rodents

Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats

New evidence of ethanol's anxiolytic properties in the infant rat

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