Does Methamphetamine (MA) Cause Cognitive and Neurological Deficits? An Ecologically Valid Approach
Description
Methamphetamine Use Disorder (MUD), which is believed to cause cognitive and neurological deficits, is a growing public health concern in the United States. However, current animal constructs of MUD do not model human use patterns. MA users ramp up to a dosage of ~0.75 mg/kg, but current animal models utilize dosages of 3-15 mg/kg. Observed cognitive and neurological deficits may be caused by neurotoxic dosages of MA, not MA use itself. To test this hypothesis, mice were injected with MA twice/day, five days/week, for six months. Dosage increased over the first month to the maintenance dose of 0.75 mg/kg. Mice were administered a cognitive pre- and post-test examining one of four cognitive functions believed to be impaired by MA abuse: cognitive flexibility (set-shift/rule reversal task), decision making (delay discounting task), long-term memory (novel object recognition task), and social cognition (social preference/social novelty task). After completion of the post-test, mice were sacrificed for immediate early gene (IEG) analysis of the caudate nucleus and nucleus accumbens, two striatal regions believed to be damaged by MA abuse. We found a small yet significant decline in IEG expression in the nucleus accumbens and caudate nucleus for nearly all conditions, a significant increase in perseverance errors in the set-shift/rule reversal task, and a significant preference for immediate rewards in the delay discounting task. All other results were insignificant. This indicates that human MA use patterns do not cause global cognitive deficits, and that other brain regions can compensate for minor striatal deficits.
Does Methamphetamine (MA) Cause Cognitive and Neurological Deficits? An Ecologically Valid Approach
Methamphetamine Use Disorder (MUD), which is believed to cause cognitive and neurological deficits, is a growing public health concern in the United States. However, current animal constructs of MUD do not model human use patterns. MA users ramp up to a dosage of ~0.75 mg/kg, but current animal models utilize dosages of 3-15 mg/kg. Observed cognitive and neurological deficits may be caused by neurotoxic dosages of MA, not MA use itself. To test this hypothesis, mice were injected with MA twice/day, five days/week, for six months. Dosage increased over the first month to the maintenance dose of 0.75 mg/kg. Mice were administered a cognitive pre- and post-test examining one of four cognitive functions believed to be impaired by MA abuse: cognitive flexibility (set-shift/rule reversal task), decision making (delay discounting task), long-term memory (novel object recognition task), and social cognition (social preference/social novelty task). After completion of the post-test, mice were sacrificed for immediate early gene (IEG) analysis of the caudate nucleus and nucleus accumbens, two striatal regions believed to be damaged by MA abuse. We found a small yet significant decline in IEG expression in the nucleus accumbens and caudate nucleus for nearly all conditions, a significant increase in perseverance errors in the set-shift/rule reversal task, and a significant preference for immediate rewards in the delay discounting task. All other results were insignificant. This indicates that human MA use patterns do not cause global cognitive deficits, and that other brain regions can compensate for minor striatal deficits.
