Planaria, a pre-clinical animal model for relapse and memory reconsolidation

The cues associated with drug of abuse are one of the reasons that trigger drug seeking and relapse even after a long abstinence. Pre-clinical studies have focused on such Pavlovian cues to understand the cognitive and neurobiological underpinnings of the mechanisms of relapse. The research of different addiction related phenomena including tolerance, behavioural sensitization and conditioned place preference (CPP) has shed light on these mechanisms; however, further investigation is still required. The studies reported here address the reinforcing effects of sucrose and cocaine on an invertebrate model using planarian flatworms. In the experiments reported here, animals were exposed to sucrose/cocaine in one context in alternation with sessions in which they received water in a different context. Test sessions in which planarians preferred a context more than the other showed the development of conditioned place preference (CPP) for the sucrose/cocaine associated context. Repeated exposure to this context in the absence of sucrose/cocaine in further test sessions led to extinction of CPP. However, extinction was achieved with different amounts of exposure in sucrose-CPP and cocaine-CPP. Cocaine-induced CPP of planarians was more resistant to extinction than CPP induced by sucrose. Re-exposure to sucrose/cocaine in a novel context after extinction reinstated the CPP response. Additional manipulations were performed to investigate the effects of an amnestic agent (Heat Shock) on reconsolidation of CPP memories in planarians. We found that expression of the acquisition (excitatory) and extinction (inhibitory) of sucrose memories in planarians depends on the length of the extinction treatment and were disrupted by the Heat Shock when administered following the extinction phase. However, the same design but administering the Heat Shock before or after a reactivation/test session caused no effect on planarians' cocaine-CPP response. Additionally, we observed that repeated exposure to sucrose resulted in tolerance: the animals developed a conditioned compensatory response. However, repeated exposure to cocaine led to behavioural sensitization, which was positively correlated with CPP learning. Consistent with the rodent literature, these results suggest that the planaria is a suitable model organism to study the mechanisms of drug addiction and formation of complex memories.