DECREASED DORSAL RAPHE NUCLEUS NEURONAL-ACTIVITY IN ADULT CHLORAL HYDRATE ANESTHETIZED RATS FOLLOWING NEONATAL CLOMIPRAMINE TREATMENT - IMPLICATIONS FOR ENDOGENOUS-DEPRESSION

Although the biological cause of endogenous depression is unknown, one commonly held hypothesis proposes that depression results, in part, f rom decreased central serotonin (5-HT) neurotransmission. Previous res earch found that clomipramine (CLI) treatment of neonatal rats produce d, in adult rats, a variety of behavioral and physiological dysfunctio ns resembling those found in human endogenous depression. It was later reported that adult CLI-treated rats exhibited a decreased discharge of 5-HT neurons in the dorsal raphe nucleus (DRN) compared with contro l rats. This finding, however, was not replicated in subsequent studie s that detected differences in DRN receptor function. Several factors were identified that may have contributed to the inability of the latt er studies to detect CLI vs. control differences in DRN firing rates a nd interspike interval histograms (ISM). Among these were the anesthet ic used, the age at which the adult rats were tested, and the location of the recording electrode. The present study controlled these variab les by using chloral hydrate anesthesia, testing 'depressed' rats at b oth 2 and 3 months of age, and verifying electrode location using stan dard histological techniques. We found that DRN unit firing in 'depres sed' rats (0.417 +/- 0.071 spikes/s) was less than half that of 'non-d epressed' control rats (i.e. neonatal saline treatment 0.968 +/- 0.12 spikes/s). Additionally, ISM's indicated that, in addition to the lowe r firing rate of 5-HT DRN neurons, adult CLI rats had an altered tempo ral discharge pattern of these neurons. Thus, the ISIH of 5-HT DRN neu rons recorded from CLI rats was characterized by a flat distribution s uggesting random temporal firing patterns. These results confirm previ ous findings of decreased DRN firing rates and flat ISM's in 'depresse d' rats and extend previous findings to younger rats of a different st rain. The results thereby lend support to the hypothesis of a role for decreased central 5-HT as a substrate for the behavioral deficiencies observed in endogenous depression and suggest that these deficiencies may also result, in part, from a random, rather than orderly, tempora l pattern of discharge in these neurons.