Abstract
These experiments examined whether morphine and cocaine alter the balance between hippocampal and striatal memory systems measured long after drug exposure. Male rats received injections of morphine (5 mg/kg), cocaine (20 mg/kg), or saline for five consecutive days. One month later, rats were trained to find food on a hippocampus-sensitive place task or a striatum-sensitive response task. Relative to saline controls, morphine-treated rats exhibited impaired place learning but enhanced response learning; prior cocaine exposure did not significantly alter learning on either task. Another set of rats was trained on a dual-solution T-maze that can be solved with either place or response strategies. While a majority (67%) of control rats used place solutions, morphine treatment one month prior resulted in the exclusive use of response solutions (100%). Prior cocaine treatment did not significantly alter strategy selection. Molecular markers related to learning and drug abuse were measured in the hippocampus and striatum one month after drug exposure in behaviorally untested rats. Protein levels of glial-fibrillary acidic protein (GFAP), an intermediate filament specific to astrocytes, increased significantly in the hippocampus after morphine exposure, but not after cocaine exposure. Exposure to morphine or cocaine did not significantly change levels of brain-derived neurotrophic factor (BDNF) or a downstream target of BDNF signaling, glycogen synthase kinase 3β (GSK3β), in the hippocampus or striatum. Thus, exposure to morphine resulted in a long-lasting shift from hippocampal toward striatal dominance during learning, an effect that may be associated with lasting alterations in hippocampal astrocytes. Cocaine produced changes in the same direction, suggesting that use of a higher dose or longer duration of exposure might produce effects comparable to those seen with morphine.