Learning and Memory Mechanisms Involved in Compulsive Drug Use and Relapse - Drugs of Abuse: Neurological Reviews and Protocols - page 84

studies should further disaggregate and redefi ne processes such as disinhibition
and attention to action (102) .

8. Habit Learning and Synaptic Plasticity
I turn now to the cellular and molecular mechanisms underlying dopamine-
modulated learning in cortex-basal ganglia circuits ( see ref. 1 ). Although the
anatomical complexities of such circuits indicate multiple potential loci for
plasticity, the cortical projections to striatum have received particular attention.
Single striatal neurons sample information from a wide array of cortical cells
(103) , and it is tempting to consider that plasticity of these synaptic connections
might readily serve as a “switchboard” linking complex stimulus representations
to behavioral responses. In this view, sets of corticostriatal synapses that are
“successful,” in the local sense of participating in driving fi ring of striatal
neurons, become temporarily eligible for persistent strengthening; if the action
in which they are participating is successful in the global sense of producing a
reinforcement signal, then such strengthening occurs. Relative to more complex
issues of motivation and goal-directed behavior, the control of habit learning
by dopamine or abused drugs thus seems intuitively (if perhaps deceptively)
straightforward to conceptualize in neurobiological terms.
Long-term potentiation (LTP) of the strength of corticostriatal connections
can readily occur in vivo (104 , 105) and stimulation of dopamine neurons
recently has been shown to modulate corticostriatal synaptic strength in direct
correlation with behavioral reinforcement (106) . Although LTP can involve a
host of cellular and subcellular mechanisms, especially in early phases (107) ,
the persistent substrate for much synaptic plasticity is generally believed to be
structural changes in synaptic connectivity patterns (108-110) . It is likely that
the persistent effects of addictive drugs on habit learning are also ultimately
manifested through altered structural patterns of synaptic connectivity (1) .
Repeated doses of amphetamine, cocaine, morphine, and nicotine can all
provoke dendritic growth and synaptic change in rat ventral striatum and PFC
(111-114) ; conversely, removal of striatal dopamine causes broad decreases in
measures of synaptic connectivity (115-118) .
In this framework the two major intracellular-level questions thus become:
(1) What is the basis of synaptic eligibility traces? and (2) How does dopamine
act to consolidate the strength of eligible synapses? In the case of hippocampal
CA3 CA1 plasticity, it has been proposed that there are certain molecules that

“tag” synapses at which coactivation of pre- and postsynaptic neurons has led
to calcium entry through N -methyl- D -aspartate (NMDA) receptors (119) ; the
identity of such molecules is unknown but is the subject of active investigation.
Persistent synaptic plasticity involves signaling to the nucleus, and transient