Inhibition of adenosine deaminase by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) mimics the effect of inescapable shock on escape learning in rats.
Three experiments examined the role of adenosine neuroregulation in the production of shuttle-escape deficits caused by prior exposure to inescapable electric shock in rats (learned helplessness). Intracerebroventricular administration of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), a selective adenosine deaminase inhibitor, mimicked the effect of earlier inescapable shock at a dose of 2.5 microM in previously restrained rats. Performance deficits produced by EHNA or by earlier exposure to inescapable shock were reversed by intraperitoneal injection of 10 mg/kg caffeine, an adenosine receptor antagonist. Finally, preexposure to an ineffective number of shocks interacted in synergy with an ineffective pretest dose (1.0 microM) of EHNA to maximize shuttle-escape latencies. These data implicate endogenous adenosine neuroregulation as a proximate mechanism in learned helplessness and conservation-withdrawal.
Woodson
J C
JC
Department of Psychology, University of California, Los Angeles, 90095-1563, USA.
Minor
T R
TR
Job
R F
RF
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000502:physiology; D058892:Adenosine Deaminase Inhibitors; D000704:Analysis of Variance; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004597:Electroshock / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004924:Escape Reaction / Q000502:physiology*; D005239:Fear / Q000502:physiology; D006380:Helplessness, Learned; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology
D058892:Adenosine Deaminase Inhibitors; D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D002110:Caffeine; C010192:9-(2-hydroxy-3-nonyl)adenine; D000243:Adenosine Deaminase; D000225:Adenine; D000241:Adenosine