ENVIRONMENTAL CONTEXT OUTWEIGHS EARLY METHAMPHETAMINE EXPOSURE IN SHAPING BEHAVIORAL AND GLUTAMATERGIC OUTCOMES IN RATS

Children prenatally exposed to methamphetamine (MA) are at high risk of developing psychiatric and behavioral disorders. Previous studies showed that the early postnatal period (days 1–12) in rats is especially vulnerable to MA. This study examined how pre-weaning and post-weaning environments affect behavior and cognition in adolescent rats exposed to MA during this sensitive period. Rat pups were administered MA (5 mg/kg) or saline from postnatal day (PD) 1 to 12, either directly or indirectly via MA-injected mothers. Two housing conditions were tested: pre-weaning (standard cages vs. enriched environment – EE) and post-weaning (single vs. group housing). Behavioral tests were conducted on PD 28–32 (habituation), PD 35–38 (object recognition/localization), and PD 40–51 (Morris water maze). Glutamate levels were measured in the striatum and hippocampus on PD 28, 35, and 48. Results indicated that direct MA administration caused more pronounced behavioral changes than indirect exposure. EE mitigated some negative effects, improving locomotion, adaptation to novelty, and altering glutamate neurotransmission. Post-weaning group housing was also beneficial, whereas individual housing impaired learning and memory, especially in late adolescence. In conclusion, both routes of drug administration and environmental conditions significantly modulate the long-term effects of early MA exposure. These findings highlight the importance of considering social and environmental factors in preclinical models to better understand how early life experiences shape cognitive and behavioral outcomes. In directly exposed animals, locomotor activity increased by approximately 20–25% compared to controls.