Biology Reference
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manner that learning of a response strategy is facilitated whereas changing strategy is
disrupted in cocaine sensitized rats (Goto and Grace, 2005b).
In Goto and Grace (2005b), DA modulation of synaptic plasticity was also considered.
Dopamine activity in the NAc is modulated by D1 and D2 receptors. Tonic and phasic DA
release was found to affect both PFC and HPC inputs into the NAc through D2 and D1
receptors, respectively. In the NAc, the dynamics of DA release were found to regulate the
balance between limbic and cortical inputs through DA receptor subtypes. During HCP
activation, increased tonic and phasic DA transmission activated D1 and D2 receptors,
changing the balance of information flow in the NAc from the PFC to the HCP. This change
facilitated the induction of LTP at HCP inputs to the NAc and LTD at PFC input to the NAc.
On the other hand, when the PFC was more highly activated and the information flow went to
the limbic structures, information processing in the NAc changed to a predominance of PFC
activity due to the induction of LTD at limbic input and LTP at cortical input. LTP at the PFC
inputs was produced only when there was a decrease in tonic D2 receptor stimulation. A
decrease in D2 receptor activity would in turn decrease D2-mediated attenuation of glutamate
release from PFC terminals (Goto and Grace, 2005b). Therefore, a decrease in DA release or
reduced expression of DA receptors, such as in repeated cocaine consumption, would change
the pattern of LTP and LTD, and hence synaptic plasticity in the NAc. The altered pattern of
synaptic plasticity could account for long-term consequences of addiction.
Studies in animals and humans have revealed that D2 dopamine receptor expression has
some role in determining individual vulnerability to the development of cocaine addiction.
Specifically, it has been reported that reduced D2 receptors is a predisposing trait for cocaine
addiction and, in turn, long-term exposure to cocaine produces a robust decrease in D2
receptor availability in primates (Nader et al., 2006) and in humans (Volkow et al.,1993,
2004). Dalley et al. (2007) reported a very interesting relationship between the levels of D2
receptor expression in rodents' NAc, behavioral impulsive traits in these animals, and their
predisposition to cocaine consumption. Lister hooded rats were examined to determine their
individual D2 receptor expression in the
NAc. Rats were classified in two groups, Impulsive
and Non-impulsive, using a five-choice serial reaction time. Impulsive rats presented a
significantly reduced D2 receptor expression in the NAc but not in the dorsal striatum. After
training the rats to self-administered cocaine, those in the Impulsive group showed a clear
tendency for escalation of intravenous cocaine self-administration (Dalley et al., 2007). These
results were consistent with those of mutant mice lacking D2-like receptors exhibiting high
rates of intravenous cocaine self-administration (Caine et al., 2002). D1 and D2 dopamine
receptor expression in the NAc could modulate the induction of LTP and LTD which in turn
change synaptic plasticity in this structure. Whether an altered innate D1/D2 dopamine
receptor balance in the NAc could have some consequences regarding synaptic plasticity in
this structure is not known. However, changes in plasticity in the NAc can induce impairment
in goal-directed behavior (Goto and Grace, 2005b). An innate reduced expression of D2
receptors could change the ratio D1/D2 in the NAc and would have consequences on the
pattern of synaptic plasticity in this structure and on individual vulnerability to escalate from
impulsive to compulsive consumption.
