Defensive-like behaviors induced by ultrasound: further pharmacological characterization in Lister-hooded rats.
BACKGROUND
In rats, dorsal periaqueductal gray (dPAG) stimulation elicits escape behavior that is thought to be related to fear and panic. A noninvasive technique--exposure to ultrasound-has been reported to stimulate the dPAG and induce escape followed by freezing in Lister-hooded (LH) rats.


OBJECTIVE
Further characterize pharmacologically the ultrasound--induced defensive behaviors test with anxiolytics acting via different mechanisms.


METHODS
LH rats, treated with clinically validated anxiolytics, putative anxiolytics, or compounds devoid of anxiolytic properties, were exposed to ultrasound. Baseline locomotion before and duration of escape and freezing behaviors during ultrasound were measured.


RESULTS
The low-potency benzodiazepine receptor agonists, diazepam and chlordiazepoxide, selectively reduced escape compared to baseline locomotor activity. The high-potency agonist alprazolam, the mGlu2/3 receptor agonist LY 354740, and the mGlu5 receptor antagonist MTEP reduced escape but did not show such a separation. The voltage-dependent calcium channel inhibitors, pregabalin and gabapentin, selectively reduced escape. The nociceptin OFQ peptide receptor agonist Ro 64-6198 did not affect escape but reduced freezing, an effect that was not produced by any of the other compounds. Buspirone and morphine did not affect escape. As expected, haloperidol reduced escape in a nonselective manner.


CONCLUSIONS
The present data demonstrate that ultrasound-induced defensive behaviors in LH rats can be independently modulated by anxiolytics of different classes. In particular, ultrasound-induced escape shows sensitivity to the majority of acute therapeutics effective in panic disorder, although sensitivity to compounds with slow onset of action (e.g., antidepressants) remains to be demonstrated.
Nicolas
Laurent B
LB
CNS Research, F. Hoffmann-La Roche Ltd., CH-4070, Basel, Switzerland.
Klein
Steffen
S
Prinssen
Eric P
EP
D000588:Amines / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology*; D000077206:Gabapentin; D006220:Haloperidol / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D000069583:Pregabalin; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors; D011957:Receptors, Opioid / Q000819:agonists; D013141:Spiro Compounds / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014465:Ultrasonics; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000094942:Nociceptin Receptor
D000588:Amines; D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D001643:Bridged Bicyclo Compounds; D002065:Buspirone; D002121:Calcium Channel Blockers; D003509:Cyclohexanecarboxylic Acids; D003975:Diazepam; D000077206:Gabapentin; D006220:Haloperidol; D007093:Imidazoles; D009020:Morphine; D000069583:Pregabalin; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D011957:Receptors, Opioid; D013141:Spiro Compounds; D013844:Thiazoles; D005680:gamma-Aminobutyric Acid; D000094942:Nociceptin Receptor; C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; C408068:Ro 64-6198; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104753:eglumetad; C000722285:Oprl1 protein, rat