Reduced LTP and LTD in prefrontal cortex synapses in the nucleus accumbens after heroin self-administration.
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ABSTRACT:
SUBMITTER: Shen H
PROVIDER: S-EPMC4349426 | biostudies-literature | 2013 Jun
REPOSITORIES: biostudies-literature
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Reduced LTP and LTD in prefrontal cortex synapses in the nucleus accumbens after heroin self-administration.
Shen Haowei H Kalivas Peter W PW
The international journal of neuropsychopharmacology 20121031 5
Addiction changes prefrontal cortex regulation of the nucleus accumbens, including reduced ability to induce long-term potentiation (LTP) and long-term depression (LTD). This important potential mechanism of impaired prefrontal regulation of behaviour has been shown only for cocaine. Here we show that animals trained to self-administer heroin demonstrate impaired LTP and LTD in the core of the nucleus accumbens following in vivo stimulation of the prelimbic prefrontal cortex. These data indicate ...[more]
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Project description:The nucleus accumbens (NAc) regulates motivated behavior by, in part, processing excitatory synaptic projections from several brain regions. Among these regions, the prefrontal cortex (PFC) and basolateral amygdala, convey executive control and affective states, respectively. Whereas glutamatergic synaptic transmission within the NAc has been recognized as a primary cellular target for cocaine and other drugs of abuse to induce addiction-related pathophysiological motivational states, the understanding has been thus far limited to drug-induced postsynaptic alterations. It remains elusive whether exposure to cocaine or other drugs of abuse influences presynaptic functions of these excitatory projections, and if so, in which projection pathways. Using optogenetic methods combined with biophysical assays, we demonstrate that the presynaptic release probability (Pr) of the PFC-to-NAc synapses was enhanced after short-term withdrawal (1 d) and long-term (45 d) withdrawal from either noncontingent (i.p. injection) or contingent (self-administration) exposure to cocaine. After long-term withdrawal of contingent drug exposure, the Pr was higher compared with i.p. injected rats. In contrast, within the basolateral amygdala afferents, presynaptic Pr was not significantly altered in any of these experimental conditions. Thus, cocaine-induced procedure- and pathway-specific presynaptic enhancement of excitatory synaptic transmission in the NAc. These results, together with previous findings of cocaine-induced postsynaptic enhancement, suggest an increased PFC-to-NAc shell glutamatergic synaptic transmission after withdrawal from exposure to cocaine. This presynaptic alteration may interact with other cocaine-induced cellular adaptations to shift the functional output of NAc neurons, contributing to the addictive emotional and motivational state.
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