title: Selective presynaptic enhancement of the prefrontal cortex to nucleus accumbens pathway by cocaine.
abstract: 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.
authors.affiliation: Molecular Neurobiology and Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, European Neuroscience Institute, 37077 Göttingen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Suska
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lee
authors.forename: Yanhua H
authors.initials: YH
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D012646:Self Administration; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D017661:Receptors, Presynaptic; D003042:Cocaine