Overview
Clinical Meaning
Neurotransmitter systems modulate every aspect of brain function, and their imbalance underlies major neurological and psychiatric disorders.
Neurotransmitter systems modulate every aspect of brain function, and their imbalance underlies major neurological and psychiatric disorders. Dopamine pathways: (1) Nigrostriatal — substantia nigra to striatum; degeneration causes Parkinson disease (bradykinesia, rigidity, tremor); (2) Mesolimbic — VTA to nucleus accumbens; hyperactivity associated with psychosis and addiction; (3) Mesocortical — VTA to prefrontal cortex; hypoactivity contributes to negative symptoms of schizophrenia and executive dysfunction; (4) Tuberoinfundibular — hypothalamus to pituitary; dopamine tonically inhibits prolactin release (antipsychotic blockade causes hyperprolactinemia). Serotonin (5-HT) is synthesized from tryptophan in raphe nuclei and modulates mood, appetite, sleep, and pain perception; deficiency is implicated in depression, anxiety, and OCD (basis for SSRI therapy). Serotonin excess causes serotonin syndrome (hyperthermia, clonus, agitation — potentially fatal). GABA is the primary inhibitory neurotransmitter; reduced GABAergic transmission lowers seizure threshold (anticonvulsants like valproate and benzodiazepines enhance GABA); GABAergic medications (benzodiazepines, barbiturates, alcohol) produce sedation, anxiolysis, and respiratory depression. Glutamate is the primary excitatory neurotransmitter; excess glutamate causes excitotoxicity (calcium influx through NMDA receptors → mitochondrial damage → cell death) in stroke, TBI, and status epilepticus. This excitotoxic cascade is the...