Reversal of neuronal and cognitive consequences of amphetamine sensitization following chronic treatment with a D1 antagonist
| Autor: | Graham V. Williams, Anita Begović, Stacy A. Castner, Lynn D. Selemon |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Psychosis Dendritic Spines Clinical Biochemistry Toxicology Biochemistry Behavioral Neuroscience Dopamine receptor D1 Cognition Neuroplasticity medicine Animals RNA Messenger Amphetamine Prefrontal cortex Biological Psychiatry Sensitization Pharmacology Neurons Receptors Dopamine D1 Antagonist Dendrites Benzazepines medicine.disease Macaca mulatta Dorsolateral prefrontal cortex medicine.anatomical_structure Memory Short-Term Dopamine Antagonists Central Nervous System Stimulants Female Psychology Neuroscience Psychomotor Performance medicine.drug Signal Transduction |
| Zdroj: | Pharmacology, biochemistry, and behavior. 96(3) |
| ISSN: | 1873-5177 |
| Popis: | Neuroplasticity is a key factor in restoration of brain function following neuropathology associated with disease or drug exposure. Here we examined the potential for chronic treatment with the selective D1 receptor antagonist SCH39166 to reverse the profound and enduring cognitive impairment associated with amphetamine (AMPH) sensitization in the nonhuman primate and to stimulate re-growth of atrophied pyramidal dendrites in the dorsolateral prefrontal cortex of these animals. Four rhesus monkeys with sustained cognitive impairment (> 1 year following AMPH sensitization) were treated for up to 8 months with SCH39166. Cognitive testing was performed before, during, and for up to 1½ year following treatment. Significant improvement in working memory performance was observed only after cessation of the D1 antagonist treatment but then was sustained for the duration of the post-treatment testing period. Postmortem quantitative assessment of Golgi-impregnated pyramidal neurons in BA9 showed that apical dendritic length and trunk spine density were increased in D1 antagonist treated monkeys relative to AMPH-sensitized and AMPH-naive monkeys. These findings, which suggest that the deleterious consequences of AMPH sensitization can be reversed by modulation of D1 receptor signaling, have implications for treating the underlying neural basis of cognitive deficits in both schizophrenia and substance abuse. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect