Chronic methamphetamine (METH) induces memory deficits that are associated with changes in hippocampal functions and plasticity factors

Abstract

METH users perform subpar than controls on tasks of verbal and nonverbal memory, recognition, attention, and decision‐making but the mechanisms that underlie these disturbances are unclear. Here we conducted memory tests in 20 male guinea pigs (200–250 g) using customized home cages and video‐tracking software. METH (10 mg/kg/day) or saline (24 μl/day) were infused using osmotic pumps for 7 days at the rate of 1.0 μl/hr. Following familiarization to 2 similar objects, in the novel object recognition test, subsequent discrimination for novel objects when tested after 3‐hours was impaired in METH‐treated guinea pigs (n=8). This impairment was still evident even after 7 days post‐drug infusion (n=8). By contrast saline controls showed discrimination for novel objects indicating good recognition memory (n=4). Molecular assays showed up‐regulation of the plasticity factors GAP‐43, BDNF and α‐synuclein in METH‐treated animals. Furthermore METH‐treated guinea pigs exhibited increased theta rhythms and decreased slow oscillations in hippocampus in vivo. Long‐term potentiation (a cellular correlate of memory) was reduced in METH guinea pigs relative to saline controls. These results suggest that METH affects some of the same processes undergirding memory functions and their drug‐induced activation partly leads to occlusion of mnemonic functions. Supported by NIH grant DA021471 & PCOM Seed Funds.