A role for delta opioid receptors in the central nucleus of the amygdala in anxiety-like behaviors.
BACKGROUND
Compounds acting on delta opioid receptors (DOR) modulate anxiety-like behaviors, yet the site of action underlying this effect is unknown. DOR mRNA and protein are expressed in the central nucleus of the amygdala, a region that plays an important role in processing fear, stress, and anxiety. We hypothesized that this brain region may contribute to the modulation of anxiety by DOR drugs.


OBJECTIVE
The present study investigated the role of DOR in the central amygdala in anxiety-like behaviors.


METHODS
The selective DOR agonist [D-Pen 2,5]-enkephalin (DPDPE) or antagonist naltrindole was bilaterally microinjected into the central nucleus of the amygdala of adult male Sprague Dawley rats and anxiety-like behaviors were assessed using the elevated plus maze. The effects of DOR agonists on heightened anxiety produced by stress were also investigated.


RESULTS
Rats injected with DPDPE into the central nucleus of the amygdala demonstrated less anxiety-like behavior, as evidenced by significantly greater number of open-arm entries and time spent in the open arms than controls. Naltrindole administered alone did not affect the duration or number of entries onto the open arms; however, naltrindole pre-treatment blocked the anxiolytic effects produced by DPDPE. Systemic administration of the selective DOR agonist, SNC80, or microinjection of DPDPE into the central amygdala prior to a swim stress blocked the anxiogenic effect produced by the swim stress.


CONCLUSIONS
These findings provide direct evidence that activation of DOR in the central amygdala reduces anxiety-like behavior and suggest that DOR in this area are important for regulating anxious states.
Randall-Thompson
Jovita F
JF
Department of Pharmacology and the Center for Substance Abuse Research, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140, USA.
Pescatore
Karen A
KA
Unterwald
Ellen M
EM
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000008:administration & dosage; D005239:Fear / Q000187:drug effects; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009292:Narcotic Antagonists / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013550:Swimming; D013997:Time Factors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole