Pain and negative affect: evidence the inverse benzodiazepine agonist DMCM inhibits pain and learning in rats.
BACKGROUND
The anxiogenic DMCM, an inverse benzodiazepine agonist, was used to explore the relationship between negative affective states and pain. Past work suggests that the outcome obtained may depend on both the intensity of the affective state and the way in which pain is inferred.


OBJECTIVE
The present study was designed to test the impact of relatively low doses of DMCM on multiple measures of pain reactivity and learning.


METHODS
In experiment 1, systemic injections of 0.00, 0.015, 0.06, and 0.25 mg/kg DMCM were administered before vocalization and tail movements were assessed in response to a gradually incremented shock and radiant heat stimulus. Experiment 2 tested the effects of DMCM on Pavlovian conditioning. DMCM-treated subjects experienced a context paired with an aversive unconditioned stimulus (US) and conditioned freezing was assessed the next day.


RESULTS
Experiment 1 showed that DMCM inhibits both a spinal nociceptive reflex (tail-flick to heat) and a supraspinal measure of pain (vocalization to shock). Because these inhibitory effects could reflect a disruption in motor function, experiment 2 employed a remote test based on Pavlovian conditioning. A moderate dose of DMCM undermined learning, implying that the drug decreased the affective impact of the aversive US.


CONCLUSIONS
DMCM induces hypoalgesia on a wide range of assays. Furthermore, pharmacologically inducing a negative affective state blocks Pavlovian fear conditioning. It is suggested that DMCM induces a state of panic and that this state inhibits pain.
Sieve
A N
AN
Texas A&M University, Department of Psychology, College Station 77843, USA. ans7657@acs.tamu.edu
King
T E
TE
Ferguson
A R
AR
Grau
J W
JW
Meagher
M W
MW
D000339:Affect / Q000502:physiology*; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004597:Electroshock; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D007858:Learning / Q000187:drug effects*; D008297:Male; D010146:Pain / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D002243:Carbolines; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate