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Amphetamines have been used as cognitive enhancers to promote learning and memory. Amphetamines are also drugs of abuse that may promote the initiation of strong memories that ultimately lead to addiction. To understand how methamphetamine (Meth) may be augmenting learning and memory, we chose a relatively simple system, the pond snail, Lymnaea stagnalis. We studied the effects of Meth exposure on the long-term memory (LTM), extinction and reinstatement of operantly conditioned aerial respiratory behavior in Lymnaea. We first determined doses of Meth that would acutely alter respiratory behavior. Next, we measured the impact of training snails in Meth solution or water (control group) using a training procedure that produces LTM (&gt;6 h) in control conditions. Meth exposure impaired the expression of LTM 21 h after two training sessions, but this appeared to be a context-dependent effect only. However, snails exposed to 3.3 mumol l(-1) Meth during training had a decreased rate of extinction of the operantly conditioned memory. We then tested whether this decreased ability of snails to extinguish memory was due to enhanced LTM or impaired extinction of that memory. Snails were operantly conditioned in water and exposed to Meth 16 h after their last trial but 4-5 h prior to extinction. Meth produced an increase rather than a decrease in extinction rate. Thus, Meth impaired extinction only when snails were exposed to Meth during training. Last, we tested the effect of Meth on the ability to form LTM using a single training procedure that is suboptimal for LTM formation. Control snails did not demonstrate LTM, as expected, but pre-exposure of snails to 3.3 micromol l(-1) Meth 24 h prior to the single training session produced LTM 24 h later, indicating that Meth pre-exposure primed snails for LTM formation. Taken together, our studies suggest that LTM is strengthened by Meth such that extinction training is less effective. Lymnaea provides a simple and useful model system to dissect the cellular and/or molecular mechanisms of how Meth may initiate the formation of stronger memories.

Methamphetamine enhances memory of operantly conditioned respiratory behavior in the snail Lymnaea stagnalis