Thyrotropin releasing hormone: Neurochemical evidence for the potentiation of imipramine effects on the metabolism and uptake of brain catecholamines

Individual differences in the exploratory activity of female hooded rats were measured in a Y-maze on two occasions, 1 week apart, before and after treatment with various tricyclic antidepressant drugs (TAD). Locomotion (maze arm entries), rearing, head-dipping into pots, and, in Experiment II only, sniffing of the pots, were scored for 5 min at each trial. In control (saline-pretreated) rats, individual differences were relatively stable over a 1-week period, as shown by small (r=0.5–0.6) but significant test-retest correlations for activity scores. In Experiment I the main finding was that positive test-retest correlations for entries and rears were abolished by short-term (6 days) pretreatment with imipramine. Also, the amount by which individual scores varied in relation to the mean tended to be reduced after imipramine, although the mean scores were unaffected. Similar effects on entries and rears were produced in Experiment II by giving a single dose of protriptyline before the second test. However, test-retest correlations for head-dipping and sniffing were unaltered, or slightly increased by protriptyline, indicating that the effects on entries and rears were not the result of a nonspecific disruption of behaviour. The effects of chlorimipramine were in contrast to those of imipramine and protriptyline. On the whole, test-retest correlations were unaffected by chlorimipramine, but in the case of Y-maze entries measured before and after short-term pretreatment with the drug, the test-retest correlation was significantly increased. These results are discussed in relation to the blocking action of TAD on the neuronal reuptake of noradrenaline and 5-hydroxytryptamine, and a parallel is drawn between the effects of imipramine and protriptyline on individual differences in animals and the therapeutic effects of these drugs in man.