Mild postnatal manipulation reduces proenkephalin mRNA in the striatum in developing mice and increases morphine conditioned place preference in adulthood

Abstract

Stressful events during certain neonatal periods may increase the vulnerability of an individual to develop psychopathology and/or drug dependence later in life. Therefore, in the present study, we assessed activity levels, emotionality, sensitivity to the effects of morphine, as well as expression of proenkephalin and prodynorphin in several brain regions in 35 and 90-day-old male mice, subjected to postnatal manipulation consisting in brief exposures to clean bedding (CB). In comparison with controls, CB mice showed reduced emotionality expressed as percentage of time in open arms of the elevated plus maze both at 35 days of life and in adulthood. Increased nociceptive threshold was also present in both time points measured. Conversely, higher locomotor activity was recorded in 35 days of life but not in adulthood. Analysis of film autoradiograms revealed no changes in prodynorphin mRNA level, but statistically significant decrease in the level of proenkephalin mRNA in striatum in young CB mice in comparison with young controls; no difference was observed between adult CB and control animals. CB adult mice also showed hypersensitivity to the rewarding effect of morphine in comparison with controls in the place preference test. In conclusion, our results revealed that in the critical period of development the effects of manipulation were evident, not only on behavioral responses but also on the neurochemical markers considered in the present research. Postnatal manipulation could induce changes in the dynamic neuronal processes occurring during development with long-term behavioral effects.