Long-term dark avoidance memory and ventral hippocampal CA1 synaptic impairments in adult rats after sub-chronic exposure to morphine during adolescence

Opioid exposure during adolescence, a critical neurodevelopmental period, can impair adult cognitive function through lasting neurobehavioral changes. Here, the effects of sub-chronic adolescent exposure to morphine (SAEM) on anxiety, fear conditioning, and synaptic plasticity in the ventral hippocampal CA1 field in adulthood were investigated. Adolescent male Wistar rats received escalating doses of morphine (2.5-12.5 mg/kg) for 5 days. Thereafter, open field and elevated plus maze tests were conducted, along with body weight was monitored during the experiment, and behavior was followed from adolescence to adulthood. Fear conditioning was performed using the passive avoidance test, and synaptic plasticity was assessed using extracellular field potential recordings in vitro. We found that SAEM did not significantly affect weight gain during the treatment period; however, it was associated with reduced weight gain in the subsequent four weeks. SAEM, specifically impaired fear conditioning and synaptic plasticity, despite showing no significant effects on locomotor activity, or anxiety-like behavior, as assessed in adulthood. Baseline synaptic responses did not differ significantly between the SAEM and control groups. However, SAEM increased the mean excitatory postsynaptic field potential (fEPSP) slopes required to produce half‑maximal population spike amplitude and reduced LTP in the ventral CA1 during adulthood. In sum, sub-chronic exposure to morphine during adolescence can persistently affect synaptic plasticity and cognitive function in adults.