Neurotrophic peptide ACTH-(4–10) permits glucocorticoid-facilitated retention of acquired immobility response of hypophysectomized rats

Abstract

The Porsolt swimming test, which was originally designed as an experimental model to screen potential antidepressants demands that rats be forced to swim for 15 min in a narrow cylinder. Twenty four hours later they are retested for 5 min during which they stay immobile for approximately 70% of the time. The present study showed that hypophysectomized animals, 14 days after operation, were unable to retain the acquired immobility. Subcutaneous glucocorticoid administration did not restore the retention of acquired immobility in contrast to our earlier finding with adrenalectomized animals. The deficit in responsiveness to glucocorticoids was eliminated when the hypophysectomized rats received ACTH-(4–10)s.c. (20 &;g/rat) every other dat. Chronic treatment with only the peptide did not improve the impaired retention of hypophysectomized rats and a single ACTH-(4–10) injection 1 day or 1 h prior to initial testing was also ineffective. We conclude that the neurotrophic peptide ACTH-(4–10) permits the expression of the glucocorticoid effect on retention of acquired immobility in the swimming test.