Molecular mechanisms of memory and drug dependence

Addiction has long been thought to include both metabolic and psychological dependence. Psychological dependence must involve long-term memory of behavioral patterns in response to specific experimental contexts. Mammalian memory, and more specifically, human memory, is largely associative. Animal models of associative memory have been provided by Pavlovian conditioning of the snail Hermissenda crassicornis and the rabbit. Striking parallels have been observed in the intrinsic molecular and biophysical transformations which accompany acquisition of the conditioned response in these different animals. In brief, associated stimuli cause elevation of Ca2+ and diacylglycerol, translocation of protein kinase C, phosphorylation of a membrane-associated G-protein, reduction of K+ currents, modification of axonal transport and structural alterations of neuronal branches. These changes can be understood and modelled as a plausible basis for memory acquisition during conditioning as well as more cognitively relevant learning such as spatial maze learning for which related neuronal alterations have recently been found. Identification of memory-specific molecular steps may help target pharmacologic agents for amelioration of learned aspects of psychiatric syndromes such as those of drug dependence.