Effects of pain- and analgesia-related manipulations on intracranial self-stimulation in rats: further studies on pain-depressed behavior.
Pain stimulates some behaviors (e.g., withdrawal responses) but depresses many other behaviors (e.g., feeding). Pain-stimulated behaviors are widely used in preclinical research on pain and analgesia, but human and veterinary medicine often rely on measures of functional impairment and pain-depressed behavior to diagnose pain or assess analgesic efficacy. In view of the clinical utility of measures of pain-depressed behaviors, our laboratory has focused on the development of methods for preclinical assays of pain-depressed behavior in rodents. The present study compared the effects of a chemical noxious stimulus (IP lactic acid injections) and an opioid analgesic (morphine) administered alone or in combination on the stretching response (a pain-stimulated behavior) and intracranial self-stimulation (ICSS; a behavior that may be depressed by pain) in rats. In the ICSS procedure, rats implanted with electrodes in the lateral hypothalamus responded to electrical stimulation across a range of current frequencies to permit rapid determination of frequency-rate curves and evaluation of curve shifts following treatment. Lactic acid alone produced a concentration-dependent stimulation of stretching and depression of ICSS, expressed as rightward shifts in ICSS frequency-rate curves. Morphine had little effect alone, but it produced a dose-dependent blockade of both acid-stimulated stretching and acid-depressed ICSS. Both lactic acid and morphine were equipotent in the stretching and ICSS procedures. These results suggest that ICSS may be useful as a behavioral baseline for studies of pain-depressed behavior.
Pereira Do Carmo
Gail
G
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
Stevenson
Glenn W
GW
Carlezon
William A
WA
Negus
S Stevens
SS
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001703:Biophysics; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D019344:Lactic Acid / Q000009:adverse effects; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000150:complications; D059408:Pain Management; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation / Q000187:drug effects* / Q000502:physiology*
D000701:Analgesics, Opioid; D019344:Lactic Acid; D009020:Morphine