Biology Reference
In-Depth Information
ERK is also involved in the neurobiological and behavioral changes occurring during
cocaine withdrawal and mediates the BDNF-induced potentiation of cocaine seeking in
response to conditioned stimuli (Lu et al., 2004). Inhibition of ERK phosphorilation in the
central amygdala (CeA) after 30 days of withdrawal decreased cocaine seeking in response to
drug cues, while stimulation of ERK activity enhanced cocaine seeking induced by cues (Lu
et al., 2004). These findings suggest that during withdrawal activation of the ERK pathway in
response to cocaine conditioned cues is involved in synaptic plasticity. The resulting synaptic
changes underlie craving and subsequent relapse during abstinence (Lu et al., 2006).
I
NSTRUMENTAL
C
ONDITIONING AND
H
ABIT
F
ORMING
IN THE
D
ORSAL
S
TRIATUM
Human drug consumption is initially a goal-directed behavior motivated by the desire to
experience the rewarding effects of the drug. Nevertheless, after repetition, this goal-directed
behavior quickly becomes a habit, a behavioral pattern that occurs automatically and nearly
involuntarily. Automatic actions are often under the control of conditioned stimuli, such as
drug-associated stimuli that have acquired the ability to motivate behavior and can trigger
craving and drug seeking in addicts.
The brain structures directly involved in the control of habits are the dorsal striatum
(caudate and putamen) and its reciprocal connection with the prefrontal cortex, which are
necessary to conduct the sequence of actions involved in habitual drug use (Everitt and Wolf,
2002; Packard and Knowlton, 2002). Whereas the ventral striatum is implicated in reward and
motivation (Cardinal et al., 2002), the dorsal striatum is implicated in cognitive control and
motor function (Packard and Knowlton, 2002), specifically the learning of stimulus-response
associations and the control of behavioral habits. The transition from declarative to automatic
behaviors proceeds efficiently without conscious involvement while the context
circumstances remain constant. If the context or the motivationally important stimulus
changes, normal individuals are able to change behavior that is no longer adaptive. In this
case, executive functions intrude to disrupt the habit in order to develop a new, more adaptive
behavior. The ability to orient towards specific goals in the environment and maintain flexible
action is a hallmark of adaptive behavior. Instrumental conditioning allows an organism to
learn contingencies between its own responses and rewarding or punishing outcomes
(Skinner, 1938; Mackintosh, 1983).
The involvement of the dorsal striatum in stimulus-reward-response has been studied
through functional neuroimaging techniques with humans. These studies have allowed the
differentiation of the role of the dorsal striatum from that of the ventral striatum, which is
involved in reward prediction (motivation). O'Doherty, using an elegant design managed to
identify the different neurobiological roles of this striatal regions. A reinforcement learning
design called advantage learning was used and a reward prediction error signal obtained and
analyzed (O'Doherty et al., 2004). Brain responses were recorded using functional resonance
imaging (fMRI). To dissociate stimulus-response (S-R) learning (instrumental) from value
prediction learning, which is one component of S-R learning, a Pavlovian conditioning task
was used. Participants have to choose between one of two stimuli: one associated with a high
probability of obtaining a reward and the other with a low probability of obtaining a reward
