Delta opioid receptor ligands modulate anxiety-like behaviors in the rat

Abstract

The role of the delta opioid receptor in regulating anxiety-like behavior in male Sprague-Dawley rats was examined. Using an elevated plus maze, the effects of the selective delta opioid receptor antagonist naltrindole (1 or 5 mg kg(-1)) and agonist SNC80 (1, 5 or 20 mg kg(-1)) on anxiety-like behavior were measured. Anxiety was also measured following administration of diazepam (3 mg kg(-1)) and amphetamine (1 mg kg(-1)) and compared to the effects of SNC80. Locomotor activity following administration of naltrindole, SNC80, diazepam, and amphetamine was measured. Finally, the defensive burying paradigm was used to confirm the findings from the elevated plus maze. Results demonstrated that SNC80 produced dose-dependent anxiolytic effects similar to that of the classical antianxiety agent, diazepam. Administration of naltrindole caused anxiogenic behavior in rats further supporting the involvement of the delta opioid receptor system in regulating anxiety. Naltrindole also blocked the anxiolytic effects of SNC80. Amphetamine had no effect on anxiety-like behavior. SNC80 induced hyperactivity similar to amphetamine at the doses tested, while naltrindole and diazepam did not significantly affect locomotor activity. Although SNC80 can increase locomotor activity, control experiments reported herein indicate that hyperlocomotion is not sufficient to produce an anxiolytic response on the elevated plus maze. Together with the results from the defensive burying paradigm, this suggests that the effects of SNC80 on reducing anxiety are independent of its effects on locomotion. Collectively these data show that the delta opioid receptor system can regulate anxiety-like behavior in an anxiolytic (agonist) and anxiogenic (antagonist) manner.

Figure 1

Effects of naltrindole (NAL, 1 or 5 mg kg⁻¹; (a, b), SNC80 (1, 5 or 20 mg kg⁻¹; (c, d) and SNC80 (5 mg kg⁻¹) antagonism by naltrindole (1 or 5 mg kg⁻¹) (e, f) on the elevated plus maze. Data are expressed as means±s.e.m. of open arm entries (a, c, e) and time on open arms (b, d, f) expressed as a percentage of the total time or number of entries (n=7–10/group). ^*P<0.05, ^**P<0.01, and ^***P<0.001.

Figure 2

Effect of SNC80 (5 mg kg⁻¹) on the defensive burying paradigm. Time spent burying a shock-probe (a) and latency to begin burying after first (b) and last (c) shock are shown. Data are expressed as the mean±s.e.m. (n=9–10/group). ^*P<0.05 and ^**P<0.01.

Figure 3

Effects of SNC80 (1, 5 or 20 mg kg⁻¹) on ambulatory activity. Activity over time (a) and during the 10 min period between 60–70 min postinjection (b) are shown. Data are expressed as the mean±s.e.m. (n=20 for saline group and n=8 for all other groups). ^***P<0.001.

Figure 4

Effects of naltrindole (NAL, 1 or 5 mg kg⁻¹; (a, b) and the combination of SNC80 (5 mg kg⁻¹) and naltrindole (1 and 5 mg kg⁻¹) (c, d) on ambulatory activity. Ambulatory activity over time (a, c) and the activity during the 10 min period between 60–70 min postinjection (b, d) are shown. Data are expressed as the mean±s.e.m. (n=20 for saline group and n=8 for all other groups). ^**P<0.01 and ^***P<0.001.

Figure 5

Effects of diazepam (3 mg kg⁻¹) and amphetamine (1 mg kg⁻¹) on an elevated plus maze (a, b) and on ambulatory activity (c, d). Data are expressed as the mean±s.e.m. (n=7–10/group for a, b; n=20 for saline group and n=8 for all other groups for c, d). ^*P<0.05, ^**P<0.01 and ^***P<0.001.