Chronic Amphetamine Abuse May Result in Long-Term Changes in Brain Activity
Recent animal studies seem to corroborate findings that rehabilitation and addiction specialists have acknowledged for years; chronic amphetamine use disrupts the emotional and cognitive processes of those who abuse it. The research in the studies cited here involved analysis of rats and rat brains that had been subjected to chronic exposure to amphetamines. This research sheds light on how the amphetamines distort and disrupt the basic processes of the brain and central nervous system.
Although amphetamines can increase attention, reaction times and focus in the short term, long-term use of the drugs can result in a chemical rewiring of those parts of the brain that mediate messages of memory, arousal, and emotional responses to environmental cues. The systems most affected by amphetamine use are those that manage and mediate D1 and D2 dopamine neurons located in the amygdala. Pathways and neuronal circuits leading from the amygdala to the prefrontal cortex seem to be hit hardest.
In the experiments reported here, rats were separated into two groups. The experimental group received moderate doses of amphetamine every other day for 10 days. A two-week washout period followed. A control set of rats was treated with saline every other day over the same timeframe. Analysis revealed that the rats treated with amphetamine exhibited less sensitivity to inhibitory messages in the amygdala and enhanced reactions to excitatory messages. The amphetamine-treated rats also displayed desensitization at D1 and D2 receptors, making them less reactive to their own stores of dopamine. They also displayed more tolerance to a later single dose of amphetamine that followed a two-week hiatus from amphetamines. The rats were also subjected to aversive conditioning and a lever pulling exercise to determine how amphetamine affected their abilities at avoiding noxious stimuli. The amphetamine-treated rats displayed degraded learning skills and learning memory when compared to the saline treated rats.
This study of rats revealed that repeated exposure to amphetamine led to disrupted connections and circuits linking the amygdala and prefrontal cortex. These alterations persisted long after discontinuation of amphetamine use. This situation caused the experimental group to forget associations between environmental cues and negative outcomes. The loss of this avoidance-memory capability prevented them from remembering the cause of something that resulted in discomfort. The fear response mechanism however was intact with the amphetamine-exposed rats. Their problems rested with their inabilities to use emotionally tied memories to guide their behaviors in response.
Addiction professionals and public safety officers have frequent contact with people who abuse amphetamines. Methamphetamine is hands-down the most notorious drug of the amphetamine family. For years, the DAR Program staff has listened to stories and anecdotes from Journal readers about how methamphetamine disrupts the cognitive abilities and behaviors of those who abuse it. These stories have often involved extraordinary reports of the behaviors of amphetamine users, behaviors that for the layperson are hard to believe. But as time goes by, the evidence is mounting that the amphetamines are uniquely harmful drugs and when taken chronically at moderate doses they pose almost certain risk to the brain. And of genuine concern from the research mentioned, this damage to the brain may be such that amphetamine abusers may not be able to rationally act and respond to the harmful consequences of their drug use. This research may help explain why methamphetamine abusers are unable to properly or emotionally react to their deteriorating faces or tooth loss that plagues them.
Tse MT et al. Repeated amphetamine exposure disrupts the dopaminergic modulation of amygdala-prefrontal circuitry and cognitive/emotional processing. Journal of Neuroscience 2011, Aug 3; 31:11282.