Endocrine and neurochemical actions of cocaine

The endocrine and neurochemical actions of cocaine in human and animal studies are reviewed. In humans, cocaine has been shown to influence plasma prolactin and growth hormone, as well as the dexamethasone suppression of cortisol and the thyroid-stimulating hormone response to thyroid-releasing hormone. In rats, cocaine affects plasma prolactin, luteinizing hormone, and testosterone, and can lead to adrenocortical hypertrophy. Behavioral sensitization to cocaine in rats has been shown to be related to the gender of the animals and appears to be modulated by vasopressin. A review of the neurochemical actions of cocaine indicates the important role of dopamine systems in the euphoric effects of the drug, as well as its withdrawal symptoms. Cocaine is a potent dopamine uptake inhibitor, as shown by its competition with [3H]GBR-12935 (a specific ligand for the dopamine uptake sites) for striatum binding sites. However, it does not acutely affect the high-affinity agonist sites of the D-2 dopamine receptors, which are suggested to be the active form of the presynaptic receptor. Using microdialysis techniques, cocaine is shown to rapidly cause a large increase of rat striatal dopamine levels, while its metabolites dihydroxyphenylacetic acid and homovanillic acid are slightly decreased and increased, respectively.