Brain dopaminergic activity

Once returned to the presynaptic terminal, dopamine is repackaged into synaptic vesicles via the vesicular monoamine transporter (VMAT) or metabolized to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO). Two alternative pathways are available for dopamine catabolism in the synapse, depending on whether the first step is catalyzed by MAO or catechol-O-methyltransferase (COMT). Thus, dopamine can be either deaminated to 3,4-dihydroxyphenylacetic acid (DOPAC) or methylated to 3-methoxytyramine (3-MT). In turn, deamination of 3-MT and methylation of DOPAC leads to homovanillic acid (HVA). In humans, cerebrospinal fluid levels of HVA have been used as a proxy for levels of dopaminergic activity within the brain (Stanley et al. 1985). 

Bonnin A, Fernandez-Ruiz JJ, Martin M, Rodriguez de Fonseca F, Flernandez ML, Ramos JA. (1993). Delta 9-Tetrahydrocannabinol affects mesolimbic dopaminergic activity in the female rat brain interactions with estrogens. J Neural Trans Gen Section. 92(2-3) 81-95. 

Antidepressants. As a rule, medicines that increase dopaminergic activity in the brain seem to work best when treating post-TBI apathy. Most antidepressants, however, work primarily by increasing serotonergic and/or noradrenergic activity. 

CS459 Navarro, M., R. de Miguel, F. Rodriguez de Fonseca, J. A. Ramos, and J. J. Femandez-Ruiz. Perinatal cannabinoid exposure modifies the sociosexual approach behavior and the mesolimbic dopaminergic activity of adult male rats. Behav Brain Res 1996 75(1-2) 91-98. 

Dopaminergic activity. Smoke was administered intranasally to mice for 20 minutes twice daily for 3 days before methamphet-amine treatment. The treatment significantly attenuated the neurotoxicity as judged by a lesser depletion of dopamine, dihydrophenylacetic acid, and homovanillic acid. The lesser effect of methamphetamine on the content of serotonin level was unaltered by prior inhalation of smoke h Tobacco glycoside, administered to mice, increased behavior via dopamine 2 neuronal activity but not dopamine 1 activity in a dose-dependent manner. The results indicated that smoking can affect the human brain function via not only the nicotinic cholinergic neuron but also the dopamine 2 neuron . 

The mechanism of deprenyl s action is unclear. In addition to enhancing dopaminergic activity in the brain by inhibiting dopamine degradation, deprenyl is metabolized into various stimulant metabolites. In spontaneously hyperactive rats used in an animal model of ADHD, chronic deprenyl administration improved im-pulsivity (but not hyperactivity or attention) along with altering levels of noradrenaline, dopamine, and serotonin and their metabolites (Boix et ah, 1998). 

Cannabinoids might alleviate some parkinsonian symptoms by their remarkable receptor-mediated modulatory action in the basal ganglia output nuclei. Moreover, it was recently observed that some cannabinoids are potent antioxidants that can protect neurons from death even without cannabinoid receptor activation. It seems that cannabinoids could delay or even stop progressive degeneration of brain dopaminergic systems, a process for which there is presently no prevention. 

The reinforcing (i.e. dependence-producing) effects of cocaine are thought to result from its ability to inhibit the reuptake of dopamine and thereby to increase dopaminergic activity, particularly in the ventral tegmental area and the nucleus accumbens, so enhancing the activity of the dopaminergic system in the mesolimbic area (the reward area) of the brain. 

Cools AR (1980) Role of the neostriatal dopaminergic activity in sequencing and selecting behavioral strategies facilitation of processes involved in selecting the best strategy in a stressful situation. Behav Brain Res 7(5) 361-378. 

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