Effect of Chronic Administration of Lithium on Memory Functions of Rats.

The psychiatric use of lithium salts in the control of mood disorders is now well established (Prien et al. 1971). There are, however, of late reports to indicate that lithium salts might exert an influence upon complex psychological functions viz. acquisition, retention and subsequent elicitation and expression of learned responses, which appear to be directly related to the drug induced changes occuring in the treatment situation. Mark and Watts (1971) and Watts and Mark (1971) demonstrated that injections into the forebrain of one day old chicks of lithium chloride prior to one trial passive avoidance learning led to impairment of the retention of subsequent avoidance responses. This effect was related to lithium induced inhibition of short term memory traces. Benowitz and Sperry (1973) found the impairment to be related to the training test interval, being more when the interval was greater. Studies involving electric shock and drug induced modification of learning and memory (McGaugh and Madsen, 1974 ; Kumar et al., 1970) indicate that short term memory traces may be largely replaced by consolidated long term traces after 20 minutes of learning which is probably what lithium affects. Benowitz et al. (Benowitz and Magnus, 1973; Benowitz and Sperry, 1973) therefore suggested that the lithium effects might be upon a behaviourally inactive, covert type of trace, distinct from the short term trace. and which functioned as a necessary precursor of long term memory. Johnson and Barker (1972) reported effects of lithium chloride on escape avoidance learning in rats, which they related to a possible drug action on processes interfering with short term memory consolidation. A series of studies utilizing the one trial aversive conditioning paradigm in chicks have been conducted at several centres and has led to the tentative identification of a sequence of events involved in the formation of memory en gram (Cherkin, 1966, 1969; Lee Teng and Sherman, 1966; Lee Teng et al., 1970; Mark and Watts, 1971; Benowitz, 1972; Benowitz and Magnus, 1973). These studies indicate that within 45 seconds of training, a relatively stable precursor to long term memory is formed (Lee Teng and Sherman, 1966). The growth of this memory trace seems to be induced by a metastable process that is activated within a fraction of a second after the aversive experience and which then persists at a constant intensity (Benowitz, 1972). Over a period of an hour or more the precursor component, which is not behaviourally accessible apparently gives rise to a permanent engram (Cherkin, 1966, 1969; Lee-Teng et al., 1970; Mark and Watts, 1971). During the same period, short term retrieval seems to be made possible by means of a distinct, electroshock sensitive form of memory (Lee-Teng et al, 1970) that has been postulated (Benowitz and