Differential contribution of cholecystokinin receptors to stress-induced modulation of seizure and nociception thresholds in mice.
Recent evidence suggest that endogenous cholecystokinin (CCK) has important roles in central responses to stress. CCK receptors are known as functional modulators of opioidergic system with a tonic antiopioid effect in nociceptive pathways. In contrast, CCK receptor ligands are known to induce anticonvulsant effects similar to endogenous opioids. It is not clear whether endogenous CCK may play a role in the anticonvulsant effects of stress, especially in those stressful paradigms that are associated with strong activation of opioid pathways. The present study examined the role of endogenous CCK receptors in acute stress-induced modulation of seizure (clonic seizures induced by pentylenetetrazole) and nociception (tail-flick) thresholds. Acute restraint stress (for 2 h) and prolonged intermittent footshock stress (30 min) both induced opioid-dependent anticonvulsant and antinociceptive effects. While CCK receptor antagonist proglumide (10, 20, or 40 mg/kg) had no effect on seizure or nociception threshold by itself, it inhibited the anticonvulsant effects of both these types of stress while potentiating their antinociceptive effects. Moreover, proglumide exerted a similar inhibition of the anticonvulsant effect and potentiation of the antinociceptive effect of acute morphine at 1 mg/kg. In contrast, brief and continuous footshock stress (3 min) that induced a nonopioid type of antinociception did not increase the seizure threshold. Proglumide pretreatment did not alter any of these effects of brief footshock stress paradigm. The present data suggest that CCK receptors specifically and differentially modulate the opioid-mediated anticonvulsant and antinociceptive effects of acute stress.
Homayoun
Houman
H
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Dehpour
Ahmad Reza
AR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D011377:Proglumide / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*
D011949:Receptors, Cholecystokinin; D011377:Proglumide