Abstract
Drug abuse and addiction are major problems in the United States. In particular methamphetamine (METH) use has increased dramatically. A greater understanding of how METH acts on the brain to induce addiction may lead to better therapeutic targets for this problem. The hippocampus is recognized as an important structure in learning and memory, but is not typically associated with drug reinforcement or reward processes. Here, the focus is on the hippocampus which has been largely ignored in the addiction literature as compared to the nucleus accumbens (NAc), ventral tegmental area (VTA), and prefrontal cortex (PFC). The results show that METH administered unilaterally via a microdialysis probe to rats’ right dorsal hippocampus will induce drug-seeking (place preference) and drug-taking (lever-pressing) behavior. Furthermore, both of these responses are dependent on local dopamine (DA) receptor activation, as they are impaired by a selective D1/D5 receptor antagonist. The results suggest that the hippocampus is part of the brain's reward circuit that underlies addiction.
Highlights
The hippocampus has not traditionally been considered part of the “reward” circuitry, previous studies demonstrate the direct involvement of the hippocampus in mediating behaviors associated with drug reward
In addition to glutamatergic input from the prefrontal cortex (PFC), the nucleus accumbens (NAc) receives glutamatergic afferents from the subiculum of the hippocampal formation (Groenewegen et al, 1987) and brief trains of electrical stimulation in the subiculum can evoke a significant increase in DA efflux in the NAc which persists for 20–30 min (Blaha et al, 1997; Taepavarapruk et al, 2000)
SELF ADMINISTRATION EXPERIMENTS Earlier, we demonstrated that the application of METH directly into the hippocampus is rewarding as measured by conditioned place preference (CPP)
Summary
The hippocampus has not traditionally been considered part of the “reward” circuitry, previous studies demonstrate the direct involvement of the hippocampus in mediating behaviors associated with drug reward. Subicular electrical stimulation has been shown to reinstate drug-seeking behavior (Vorel et al, 2001; Taepavarapruk and Phillips, 2003) whereas hippocampal-subicular pharmacological inactivation reduces drug-seeking and drug-taking behavior in rodents (Sun and Rebec, 2003; Black et al, 2004). Using another classic model of reward, it was shown that morphine infusions into hippocampus induces a conditioned place preference (CPP) in rats (Corrigall and Linseman, 1988). Associating context-spatial locations with drug rewards is fundamental to survival in natural environments and requires the integrity of the hippocampus and ventral striatum (Lansink et al, 2009)
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