A second publication for Optopath in Neuropsychopharmacology
Cocaine seeking: The dual role of the prelimbic cortex in High frequency users.
Coupling cocaine intravenous self-administration with optogenetic, Dr Deroche-Gamonet in collaboration with Dr Herry reveals that high frequency cocaine intake promotes a PL-dependent control of cocaine seeking, with the PL exerting a facilitatory effect on cocaine-induced resinstatement and an inhibitory effect on cocaine self-administration. Individual differences in cocaine-induced PL activation might be a source of vulnerability for poorly controlled cocaine-induced seeking and/or cocaine intake.
Martín-García E, Courtin J, Renault P, Fiancette JF, Wurtz H, Simonnet A, Levet F, Herry C, Deroche-Gamonet V. Frequency of Cocaine Self-Administration Influences Drug Seeking in the Rat: Optogenetic Evidence for a Role of the Prelimbic Cortex. Neuropsychopharmacology. 2014 Mar 17. doi: 10.1038/npp.2014.66. [Epub ahead of print]
High frequency intake and high drug-induced seeking are associated with cocaine addiction in both human and animals. However, their relationships and neurobiological underpinnings remain hypothetical. The medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and nucleus accumbens (NAc) have been shown to play a role in cocaine seeking. However, their involvement in regulating high frequency intake and high cocaine-induced seeking is unclear. We manipulated frequency of cocaine self-administration and investigated whether it influenced cocaine seeking. The contribution of the aforementioned structures was evaluated using changes in expression of the immediate early gene c-Fos and targeted optogenetic manipulations. Rats that self-administered at High frequency (short inter-infusion intervals allowed by short time-out) showed higher cocaine-induced seeking than Low frequency rats (long inter-infusions intervals imposed by long time-out), as measured with cocaine-induced reinstatement. c-Fos was enhanced in High frequency rats in the prelimbic (PL) and infralimbic (IL) areas of the mPFC, the BLA, and the NAc core and shell. Correlational analysis of c-Fos revealed that the PL was a critical node strongly correlated with both the IL and NAc core in High frequency rats. Targeted optogenetic inactivation of the PL decreased cocaine-induced reinstatement, but increased cocaine self-administration, in High frequency rats. In contrast, optogenetic activation of the PL had no effect in Low frequency rats. Thus, High frequency intake promotes a PL-dependent control of cocaine seeking, with the PL exerting a facilitatory or inhibitory effect, depending on operant contingencies. Individual differences in cocaine-induced PL activation might be a source of vulnerability for poorly controlled cocaine-induced seeking and/or cocaine intake.