Ja. Kiritsyroy et al., SPINAL ANTINOCICEPTION MEDIATED BY A COCAINE-SENSITIVE DOPAMINERGIC SUPRASPINAL MECHANISM, Brain research, 644(1), 1994, pp. 109-116
The role of dopaminergic descending supraspinal processes in mediating
the antinociceptive action of cocaine was studied in the rat using a
combination of extracellular neuronal recording and behavioral techniq
ues. Neurons in the superficial laminae (I-II) of the spinal dorsal ho
rn with receptive fields on the tail were recorded in anesthetized rat
s using insulated metal microelectrodes. Stimulation of the receptive
field with either high intensity transcutaneous electrical pulses or w
ith an infrared CO2 laser beam produced a biphasic increase in dorsal
horn unit discharge. Conduction velocity estimates indicated that the
early discharge corresponded to activity in A delta whereas the late r
esponse corresponded to activity in C afferent fibers. Cumulative dose
s of cocaine (0.1-3.1 mg/kg i.v.) inhibited the late response to eithe
r electrical or laser stimulation in a dose-related manner. The early
response to laser, but not electrical, stimulation was also suppressed
by cocaine. Neurons in the spinal dorsal horn with receptive fields o
n the ipsilateral hindpaw were activated by natural noxious (pinch) or
innocuous (tap) somatic stimulation. Cocaine selectively suppressed n
ociceptively evoked dorsal horn unit discharge. This antinociceptive e
ffect was dose-related (0.3-3.1 mg/kg, i.v.) and antagonized by eticlo
pride (0.05-0.1 mg/kg, i.v.), a selective D2 dopamine receptor blocker
. The same doses of cocaine failed to inhibit the responses of dorsal
horn neurons to low threshold innocuous stimulation. Complete thoracic
spinal cord transection eliminated the antinociceptive effect of coca
ine on dorsal horn neurons and also eliminated the cocaine-induced att
enuation of the tail-flick reflex. These data demonstrate that cocaine
selectively inhibits nociceptive spinal reflexes and the nociceptive
responses of dorsal horn neurons primarily by means of a D2 dopaminerg
ic receptor mechanism. This antinociceptive effect of cocaine is indep
endent of its local anesthetic activity and requires the integrity of
the thoracic spinal cord, suggesting that the drug potentiates or acti
vates supraspinal dopaminergic projections to the dorsal hem.