Behavioural and Pharmacological Assessment of Addiction in Planaria

Animal models of learning and memory can provide useful insights into how humans learn and retain new information. This is important for understanding the roles of learning and memory in addiction. Animals repeatedly exposed to rewarding substances in the presence of environmental cues learn to associate such cues with the reward. Subsequent repeated exposure to these cues in the absence of the reward leads to extinction of the previously learned behaviour. However, re-exposure to the rewarding substance leads to the reinstatement of the previously extinguished conditioned response. The experiments reported in this thesis determined whether these effects, commonly observed in rodents, are evident in invertebrates, specifically, planaria. Planaria were exposed to sucrose in one context in alternation with trials in which they were exposed to water in a different context. Test trials in which animals chose between contexts indicated the development of conditioned place preference (CPP) for the context associated with sucrose. Repeated test trials without sucrose led to extinction of CPP. Re-exposure to sucrose in a novel context after extinction, reinstated CPP. Further data showed that the development of the appetitive response (e.g., CPP) depended on the dopamine reward system. Additional experiments investigated how repeated exposure to a reward with specific environmental cues led to the development of tolerance and the establishment of a conditioned compensatory response. The development of tolerance or the conditioned compensatory response was independent of the dopamine system. Following this basic finding, the role of the cholinergic system in these learning mechanisms, specifically the encoding and reconsolidation of learned information, were assessed. Treatment with atropine (a muscarinic acetylcholine receptor antagonist) prevented memory consolidation and interfered with memory reconsolidation. These results suggest that addiction to sucrose can be characterised as a learned response in planaria, one that depends upon the principles and mechanisms that rule associative learning in rodents. Such findings may provide the basis for pre-clinical models of learning and memory with future applications in the treatment of addiction and obesity

Dissociation of place preference and tolerance responses to sucrose using a dopamine antagonist in the planarian.

In rodents, sucrose has been found to elicit addictive-like behaviours like the development of tolerance and the association with cues present at the time of consumption. Furthermore, the neurochemical response to sucrose binges is equivalent to the one observed in response to the abuse of addictive substances like cocaine. The experiments reported here address the effects of sucrose on an invertebrate model, the Platyhelminth brown planarian. The animals exposed to a 10% sucrose solution in one context developed a conditioned place preference (CPP) which was subsequently extinguished in the absence of the rewarding agent. However, one exposure to sucrose per se sufficed to reinstate the CPP response, suggesting sucrose-induced CPP can be characterised as a standard Pavlovian response. The same training procedure led to the development of context-specific tolerance to the effects of sucrose. However, comparing animals treated with dopamine D1 antagonist (SCH-23390) with control animals showed that the establishment of CPP, but not the development of tolerance, is mediated by the dopamine reward system