Crf1-receptor antagonist cp-154526 reduces alerting-related cutaneous vasoconstriction in conscious rabbits

Abstract

Cutaneous vasoconstrictor responses elicited by salient stimuli in conscious rabbits may be a sensitive physiological index of emotional arousal/anxiety. Ear-pinna blood flow was measured by preimplanted laser Doppler probes, and animals were exposed to situations involving different types of potentially salient stimuli before and after i.v. administration of CP-154526 (15 mg/kg) or diazepam (4 mg/kg). At rest, ear-pinna blood flow was stable (coefficient of varition=11 ±2) and remained at high level 93±13% of test time. Exposure to novel environment elicited flow fluctuations (coefficient of variation=79 ±8) and reduced amount of time spent at high level to 25 ±6%. Defined unconditioned stimuli caused rapid falls in ear-pinna flow, with nociceptive stimulation producing more vigorous and consistent effects (flow response index 0.66 ±0.02) compared with non-nociceptive (flow response index 0.49 ±0.04). CP-154526 slightly raised mean arterial pressure (from 81±2 to 93±3 mmHg), increased heart rate (from 198±1 to 220±4 beats/min) and produced a mild vasoconstriction in the ear-pinna bed (flow fell from 46±10 to 25±6 cm/s). CP-154526 substantially reduced cutaneous vasoconstrictor responses elicited by the exposure to novel environment and by defined non-nociceptive stimuli, with flow-response index fall from 0.53±0.10 to 0.17±0.09 and from 0.47±0.04 to 0.24±0.04, respectively, without affecting responses to nociceptive stimuli. Diazepam reduced only vasoconstrictor responses elicited by the exposure to novel environment, with flow-response index fall from 0.40±0.12 to 0.27±0.07. Sensitivity of rapid changes in rabbit ear-pinna blood flow to anxiolytic drugs supports the idea that increased cutaneous vascular tone reflects enhanced arousal in rabbits.