Olfactory Bulbectomy in Methamphetamine-Treated Rat Mothers Induces Impairment in Somatic and Functional Development of Their Offspring

Abstract

Olfactory bulbectomy in rodents is considered a putative model of depression. Depression is often associated with drug addiction. Our previous studies demonstrated that methamphetamine (MA) administration to rat mothers affects both, mothers and their pups. The aim of the present study was to examine the effect of bulbectomy, as a model of depression, and MA administration on behavior of rat mothers and postnatal development of their pups. Adult female Wistar rats were randomly divided into two groups: bulbectomized (OBX) and sham-operated (SH). A period of 20 days was allowed for the development of the depressive-like phenotype. Animals were tested in the motor activity test and 2 % sucrose preference for anhedonia and hyperactive locomotor response to a novel environment, respectively. After then females were impregnated. Pregnant females were exposed to daily subcutaneous (s.c.) injection of MA (5 mg/kg) or saline (SA) during the entire gestation period. Postnatally, maternal behavior and pup development was examined. The effect of a challenge dose of MA (1 mg/kg, s.c.) on behavior was further examined in adult male offspring. Our results showed no differences in the maternal behavior as a matter of bulbectomy, only OBX rats slept more than all the SH controls. Pups from OBX mothers were born with lower birthweight and gained less weight during the postnatal development than pups from SH controls. Both, bulbectomy and MA administration, delayed the eyes opening. As a matter of functional development of the pups, maternal OBX procedure impaired the performance in the Bar-holding test, but only in saline group. OBX/SA group was the worst in the Bar-holding test relative to all the other groups. In addition, pups from OBX mothers dropped more boluses during the Bar-holding test, suggesting that they were more stressed. In adult male offspring, bulbectomy increased immobility only in the SA/SA group. Prenatal MA exposure increased locomotion, while decreasing immobility. In addition, challenge dose of MA in adulthood increased distance traveled, locomotion, rearing, and average and maximal velocity, while decreasing immobility and grooming. In conclusion, our results suggest that depressive-like phenotype of rat mothers induces impairment in somatic and functional development of their male offspring.