Learning and Memory Mechanisms Involved in Compulsive Drug Use and Relapse - Drugs of Abuse: Neurological Reviews and Protocols - page 80

However, dopamine affects not just plasticity of circuits through striatum,
but also expression of already established striatum-dependent behaviors.
The ability to respond to salient stimuli, whether internally or externally
generated, relies on the presence of striatal dopamine; complete loss of striatal
dopamine causes severe Parkinson's disease in humans and experimental
animals. Conversely, events that are generally “arousing”—including rewards,
stressors, and novelty—can provoke increases in dopamine release lasting
minutes or more ( see references in ref. 72 ). Dopamine thus clearly has an
important role in psychomotor activation and attentional processes. The
relationship between slow and fast shifts in dopamine release remains poorly
understood—despite a long-standing recognition of the importance of distin-
guishing phasic and tonic dopamine release (73) .
6. Addictive Drugs and Learning Processes
Striatal dopamine is also elevated by drugs of abuse. Indeed, although such
drugs have a wide variety of effects in numerous parts of the brain, the shared
ability to enhance striatal dopamine release remains the best candidate for a
key common action ( see references in ref. 1 ). The mechanisms by which drugs
produce altered striatal dopamine release are varied—for example, nicotine
likely achieves this both through actions on midbrain dopamine neurons (74)
and through local modulation of dopamine release in striatum (75) . By altering
release of dopamine throughout the striatum, drugs of abuse can alter both
acute information-processing and long-lasting plasticity across a wide range
of cortex-basal ganglia circuits. If striatal dopamine can act as a reinforcement
learning signal, then it makes sense that self-administration of drugs that
elevate dopamine is reinforced. In fact, multiple kinds of learning contribute
to any given drug's reinforcing properties (76 , 77) . Besides affecting a range
of cortex-basal ganglia circuits, abused drugs can also affect neuromodulators
in other brain systems important for motivated behavior, such as hippocampus
and amygdala (78) .
Dopaminergic modulation of cortex-ventral striatal circuits appears to be
important for “rewarding” sensations. The deliberate desire to repeat such
experiences doubtless underlies much human drug use. However, some drugs
such as nicotine produce mild, if any, pleasant sensations during initial use,
and yet can be highly addictive. The ability of drugs to affect other aspects
of reinforcement may therefore be of greater importance to addiction than
their rewarding effects. For example, Viaud and White (79) found that local
amphetamine injections directly into striatal regions that receive visual cortical
inputs enhance learning of a visually conditioned response, while injections into