Multi-dimensional analysis of behavior in mice treated with the delta opioid agonists DADL ( d-Ala 2- d-Leu 5-enkephalin) and DPLPE ( d-Pen 2- l-Pen 5-enkephalin)

Abstract

The effects of intracerebroventricular injection of the delta-selective opioid peptides, DADL ( d-Ala 2- d-Leu 5-enkephalin) and DPLPE ( d-Pen 2- l-Pen 5-enkephalin), on spontaneous locomotor activity were investigated in mice using multi-dimensional behavioral analysis, based upon a capacitance system. The analysers classified the movements into 9 sizes ( 1 1 , 1 2 , 1 4 , 1 8 , 1 16 , 1 32 , 1 64 , 1 128 and 1 256 ) . Specific patterns of behavior were each registered on these sizes of movement. At 1.0 and 3.0 μg, DADL produced a significant increase in circling ( 1 4 size of movements) within 15 min after the start of measurements, while it produced a marked increase in linear locomotion ( 1 2 size), circling ( 1 4 size), rearing ( 1 16 size) and grooming ( 1 32 , 1 64 and 1 128 sizes) within 15–30 min after the start. At 10.0 μg, DPLPE decreased linear locomotion ( 1 1 size) and conversely increased circling behavior ( 1 4 size) within 15 min after the start, whilst this peptide at 3.0 or 10.0 μg, produced a marked increase in linear locomotion ( 1 2 size), circling ( 1 4 size) and grooming ( 1 128 size) within 15–30 min after the start. The behavioral effects induced by DADL (3.0 μg) and DPLPE (10.0 μg) were completely reversed by naloxone (1.0 and 2.0 mg kg ). These results obtained with DPLPE, a delta-selective peptide and DADL, a less delta-selective peptide, indicate a common pattern of activity which was presumably delta receptor-mediated. However, one component (linear locomotion, at times immediately after administration of the peptide) did clearly differ between these two peptide analogues. It is suggested that the depression of linear locomotion by DPLPE is delta receptor-mediated and that, in the case of DADL, its affinity for mu receptors might act to mask this action. These data, moreover, demonstrate the value of using multiple parameters in assessing the differences of selective vs nonselective opioid receptor agonists in vivo.