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

Abstract

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.

Moderate ethanol exposure during early ontogeny of the rat alters respiratory plasticity, ultrasonic distress vocalizations, increases brain catalase activity, and acetaldehyde-mediated ethanol intake

“…In addition, pups showed lower breathing frequencies until an apneic episode occurred (coefficient breaths/apneas, Figure 2C ). Regardless of the treatment’s nature, a transient decrease in breathing frequencies ( Figure 2A ) was observed throughout evaluations, indicative of a habituation process ( Macchione et al, 2016 , 2018 , 2021 ; Acevedo et al, 2017a , b ; D’aloisio et al, 2020 ; Trujillo et al, 2020 ). The short and long-term effects of ethanol on neonatal respiratory plasticity more recently have received attention given the association between fetal alcohol exposure and the sudden infant death syndrome ( Iyasu et al, 2002 ; Burd et al, 2004 ; Bailey and Sokol, 2011 ; O’Leary et al, 2013 ).…”

“…Under the present experimental conditions, we were unable to observe a role of gestational acetaldehyde upon respiratory plasticity or affective state of the organisms. To our knowledge, there is one study that reports respiratory depressions following acetaldehyde central administration 5 minutes, but not 60 or 120 after (Acevedo et al, 2017b). As to the role of acetaldehyde in the modulation of ethanol's affective state, the results in adult rodents are controversial and seem to depend on factors such as the dose, route of administration, or animal strain.…”

“…One basal minute was considerate to allow air pressure stabilization. These experimental procedures have been previously used to assess breathing patterns as function of ethanol exposure during pre- and postnatal period ( Cullere et al, 2015 ; Macchione et al, 2016 , 2018 , 2021 ; Acevedo et al, 2017a , b ; D’aloisio et al, 2020 ; Anunziata et al, 2021 ).…”