Abstract
Rationale
Animal studies indicate that central acetaldehyde, dependent on catalase metabolism of ethanol (EtOH), modulates ethanol reinforcement. Brain catalase activity and acetaldehyde (ACD) production are significantly higher in rat pups compare d with adults. Interestingly, infant rats show high EtOH affinity for alcohol consumption and are particularly sensitive to the drug’s reinforcing effects.
Objectives
We tested whether central ACD is necessary and sufficient to induce appetitive conditioning in newborn rats through the artificial nipple technique.
Methods
Vehicle, EtOH (100 mg%), and acetaldehyde (0.35 μmol) were administered into the cisterna magna (1 μl). Half of the animals also received a central administration of 75 μg (experiment 1) or 40 μg of d-penicillamine (experiment 2). Afterwards, pups were exposed to an olfactory cue (conditioned stimulus). One hour later, neonates were tested with an artificial nipple in the presence of the conditioned cue. Nipple attachment duration, mean grasp duration, and number of nipple disengagements served as dependent variables.
Results
Positive responses to the scented nipple occurred in neonates conditioned with EtOH or ACD (experiments 1 and 2). In experiment 1, there were indications that d-penicillamine weakened the reinforcing effects of EtOH and ACD. In experiment 2, d-penicillamine (40 μg) significantly inhibited appetitive conditioned responses dependent upon EtOH or ACD.
Conclusions
Appetitive conditioning was observed when employing either central EtOH or ACD as unconditioned stimuli. Central abduction of ACD inhibited conditioned appetitive responsiveness to the surrogate nipple. Central ACD is involved in the determination or modulation of EtOH’s motivational properties during early stages in development.
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Acknowledgments
This work was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica (FONCyT, PICT 05-254) awarded to J.C.M., by the Secretaría de Ciencia y Técnica from Universidad Nacional de Córdoba awarded to S.M. March, and by grants from NIAAA (AA11960, AA013098, AA015992) and NIMH (MH035219) awarded to N.E.S. The authors would like to thank José I. Hernández for the technical assistance.
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March, S.M., Abate, P., Spear, N.E. et al. The role of acetaldehyde in ethanol reinforcement assessed by Pavlovian conditioning in newborn rats. Psychopharmacology 226, 491–499 (2013). https://doi.org/10.1007/s00213-012-2920-9
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DOI: https://doi.org/10.1007/s00213-012-2920-9