Affective analgesia following muscarinic activation of the ventral tegmental area in rats.
Cholinergic stimulation of dopamine neurons in the ventral tegmental area (VTA) underlies activation of the brain reward circuitry. Activation of this circuit is proposed to preferentially suppress the affective reaction to noxious stimulation. Vocalization afterdischarges (VADs) are a validated model of the affective response of rats to noxious tail shock. The antinociceptive action of the acetylcholine agonist carbachol microinjected into the VTA on VAD threshold was compared with its effect on the thresholds of other tail shock-elicited responses (VDS, vocalizations during shock; SMR, spinal motor reflexes). Whereas VADs are organized within the forebrain, VDSs and SMRs are organized at medullary and spinal levels of the neuraxis, respectively. Carbachol (1 microg, 2 microg, and 4 microg) injected into VTA produced dose-dependent increases in VAD and VDS thresholds, although increases in VAD threshold were significantly greater than increases in VDS threshold. Administration of carbachol into VTA failed to elevate SMR threshold. Elevations in vocalization thresholds produced by intra-VTA carbachol were reversed in a dose-dependent manner by local administration of the muscarinic receptor antagonist atropine sulfate (30 microg and 60 microg). These results provide the first demonstration of the involvement of the VTA in muscarinic-induced suppression of pain affect.


CONCLUSIONS
Cholinergic activation of the brain reward circuit produced a preferential suppression of rats' affective reaction to noxious stimulation. The neurobiology that relates reinforcement to suppression of pain affect may provide insights into new treatments for pain and its associated affective disorders.
Kender
Robert G
RG
Department of Psychology, Behavioral and Cognitive Neuroscience Program, Wayne State University, Detroit, Michigan 48202, USA.
Harte
Steven E
SE
Munn
Elizabeth M
EM
Borszcz
George S
GS
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects / Q000379:methods; D008297:Male; D008845:Microinjections / Q000379:methods; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012054:Reinforcement, Psychology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013623:Tail / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology; D014828:Vocalization, Animal / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D018678:Cholinergic Agents; D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D001285:Atropine; D002217:Carbachol