Results demonstrate that in vivo and in vitro cocaine exposure differentially modulate potentiation in the CA1 region of rat hippocampal tissue slices in vitro. First, in the acute presence of relatively high cocaine concentrations, long-term potentiation (LTP) is significantly reduced as compared to naive control potentiation; conversely, potentiation is significantly facilitated in the presence of lower cocaine concentrations. Upon washout of the drug, LTP remains significantly augmented. When rats chronically ingest cocaine in an in vivo behavioral paradigm, LTP is also modulated such that three days after the animals' last exposure, potentiation is significantly facilitated, as compared to controls; however, when the brain tissue is harvested approximately three months after, LTP is significantly depressed. The mechanisms of action mediating these chronic biphasic effects within the hippocampus have yet to be fully elucidated. It is commonly accepted that cocaine's euphoric effects are due to the inhibition of dopaminergic, noradrenergic, and serotonergic transporters; coincidently, these monoamines also function in modulating LTP within the hippocampus. Hence, we investigate the possibility of a link between the two.; The ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC) are three primary components of the mesolimbic dopaminergic pathway and are thought by many to be involved in the rewarding aspects of illicit drug abuse. Each of these brain structures is also innervated by glutamatergic efferents from the hippocampus; recently, evidence within the literature has also suggested that dopamine (possibly from the ventral tegmental area) may play a role in the induction and expression of LTP in the hippocampus. It is thus hypothesized that monoaminergic regulation in the hippocampus may ultimately affect the associative learning and memory mechanisms involved with the positive reinforcement of drug use as well as craving and relapse.
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