Dopamine/dopaminergic system amphetamines

Both amphetamine and cocaine have also been reported to support intracranial self-administration in the mesolimbic/mesocortical dopaminergic system. Rats will self-administer cocaine into the medial prefrontal cortex (Goeders and Smith 1983). while amphetamine is self-administered into the orbitofrontal cortex of rhesus monkeys (Phillips and Rolls 1981) and the nucleus accumbens of rats (Hoebel et al. 1983 Monaco et al. 1981). These data indicate that the mesolimbic/mesocortical dopaminergic system is involved in the initiation of stimulant reinforcement processes, and this work suggests that the region of the nucleus accumbens, more specifically the mesolimbic dopamine system, may be an important substrate for reinforcing properties of several psychomotor stimulant drugs. 

According to Carpenter, Conley, and Buchanan (1998), stimulants such as cocaine and amphetamines activate the dopaminergic system in the brain, which explains why the abuse of stimulants can induce a paranoid psychosis that mimics the positive symptoms representative of schizophrenia. In turn, if a person who is diagnosed with schizophrenia is given stimulants of this type, the psychosis may be exacerbated. It follows, therefore, that the typical antipsychotic medications act by blocking the dopamine receptors. 

The mesolimbic dopaminergic system is the principal reward pathway in the brain. Amphetamine, cocaine, and opiates cause dopamine release in the nucleus accumbens. Food seeking and sexual behavior do so as well. 

Amphetamine blocks the uptake of dopamine, 5-HT, and norepinephrine by presynaptic transporters, increasing the extracellular levels of these monoamines. D-amphetamine acts primarily on the dopaminergic systems, wdiereas L-amphetamine acts primarily on norepinephrinergic neurons. The stimulant effects of D-amphetamine on behavior are linked to enhanced dopaminergic activity, primarily in the mesolim-bic system of neurons. 

Several lines of evidence have suggested the interactions of ascorbic acid with dopaminergic systems. Like the dopamine antagonist haloperidol, intraventricular or intrastriatal infusions of ascorbic acid (White et al, 1988, 1990) have been shown to attenuate the behavioral response to amphetamine, indicating that at some level ascorbic acid antagonizes the synaptic action of dopamine. Ascorbic acid also has been shown to mimic haloperidol in producing behavioral supersensitivity to... 

The nucleus accumbens is part of the limbic system. It receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area (A 10 cell group). This mesolimbic dopaminergic pathway is part of the reward pathways. Drugs of abuse (cocaine, amphetamine, opiates or nicotine) have been shown to increase the level of dopamine release in these neurons. 

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

A model for the action of cocaine and amphetamine at a dopaminergic synapse in the central nervous system. Cocaine (right side) blocks the dopamine reuptake transporter (DAT). Amphetamine (left side) has several effects. It enters the nerve ending via reverse transport by the DAT and displaces dopamine (DA) from vesicles by altering their pH. It also inhibits dopamine metabolism by MAO in the nerve ending. The increased intraneuronal dopamine causes reversal of the DAT and dopamine floods into the synapse. 

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