On 2014 May 26, Serge Ahmed commented:

This clever study shows that responding for cocaine-associated cues can be entirely and persistently abolished by canceling out cocaine-induced long-term plasticity at hippocampal and cortical synaptic inputs to D1R-expressing neurons in the nucleus accumbens. Importantly, the latter feat was achieved by acutely co-opting endogenous mechanisms of synaptic plasticity using astute optogenetic-based LTD protocols.

The efficacy of these LTD protocols was specific to responding for cocaine-associated cues and had no impact on responding for sucrose or sucrose-associated cues - which were both notably more intense and more robust than responding for cocaine-associated cues.

One may regret that the authors did not test whether and to what extent the same LTD protocol that acutely abolished responding for cocaine-associated cues would also affect the maintenance of responding for cocaine itself and/or the ability of other well-known factors to trigger “relapse.” These additional experiments would have been helpful to better define what has exactly been erased by the LTD protocols. It would also be important to know whether the same efficacy could be achieved after more prolonged exposure to cocaine self-administration.

Finally, this study paradoxically shows that endogenous mechanisms of synaptic plasticity are apparently largely intact in cocaine-exposed animals and can be co-opted to reverse, persistently and rather easily, cocaine-induced synaptic plasticity. One may then wonder whether and to what extent similar mechanisms could be self-recruited by people who successfully quit cocaine.

On 2014 May 26, Serge Ahmed commented:

This clever study shows that responding for cocaine-associated cues can be entirely and persistently abolished by canceling out cocaine-induced long-term plasticity at hippocampal and cortical synaptic inputs to D1R-expressing neurons in the nucleus accumbens. Importantly, the latter feat was achieved by acutely co-opting endogenous mechanisms of synaptic plasticity using astute optogenetic-based LTD protocols.

The efficacy of these LTD protocols was specific to responding for cocaine-associated cues and had no impact on responding for sucrose or sucrose-associated cues - which were both notably more intense and more robust than responding for cocaine-associated cues.

One may regret that the authors did not test whether and to what extent the same LTD protocol that acutely abolished responding for cocaine-associated cues would also affect the maintenance of responding for cocaine itself and/or the ability of other well-known factors to trigger “relapse.” These additional experiments would have been helpful to better define what has exactly been erased by the LTD protocols. It would also be important to know whether the same efficacy could be achieved after more prolonged exposure to cocaine self-administration.

Finally, this study paradoxically shows that endogenous mechanisms of synaptic plasticity are apparently largely intact in cocaine-exposed animals and can be co-opted to reverse, persistently and rather easily, cocaine-induced synaptic plasticity. One may then wonder whether and to what extent similar mechanisms could be self-recruited by people who successfully quit cocaine.