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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

the glutamate receptors are coupled to sodium channels and therefore
can mediate rapid (approximately 1 millisecond) actions, whereas other
receptors are coupled to potassium channels through a G protein, and
therefore take approximately 1 second for response. Glutamate is
important for learning and plays an essential role in the hippocampus.
Hallucinogens, such as phencyclidine (PCP) act at the NMDA subtype of
glutamate receptor. In addition, it is thought that glutamate pathways play
a very important role in modulating neural responses to many other
psychoactive substances.

Dopamine

Dopamine is a neurotransmitter that is derived from the amino acid
tyrosine, and is structurally related to norepinephrine. Dopamine produces
inhibitory postsynaptic potentials. It is involved in movement, learning and
motivation. Dopamine plays a paramount role in the neurobiology of
dependence, and will be discussed in more detail in Chapters 3 and 4.
Dopamine receptor genes have also been highly implicated in substance
dependence in general, as well as in nicotine and alcohol dependence. There
are two major dopamine projections in the brain. One, the mesolimbic
pathway, projects from the VTA to the nucleus accumbens. This pathway
appears to be directly or indirectly activated by most known psychoactive
substances. Closely associated with this is the mesocortical dopamine
pathway, which projects from the VTA to regions of the cortex. The second
major dopamine pathway projects from the substantia nigra to the striatum,
which is known as the nigrostriatal pathway. In Parkinson disease, this
pathway undergoes degeneration leading to the characteristic movement
disorders. Excessive dopamine function in the mesolimbic and mesocortical
dopamine systems is thought to underlie the delusions and hallucinations
of schizophrenia. It is interesting to note here that certain substances such
as cocaine and amphetamine can, in high doses, mimic some of the features
of schizophrenia and bipolar disorders through the same basic actions on
the dopamine system.

Norepinephrine
Norepinephrine is another catecholamine that is derived from tyrosine.
Norepinephrine-synthesising cell bodies are found in the locus coeruleus,
and project widely throughout the brain. Norepinephrine is involved in
arousal and stress responses. Cocaine and amphetamine affect the
transmission of norepinephrine by increasing its concentration in the
synaptic cleft. This increase in synaptic norepinephrine contributes to the
stimulatory and rewarding effects of cocaine and amphetamine, and also to
the feelings of nervousness and anxiety that can accompany the use of these
substances.

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