Morphine acts in the parabrachial nucleus, a pontine viscerosensory relay, to produce discriminative stimulus effects.
Morphine is known to act centrally to produce discriminative stimulus effects, but the specific neuroanatomical sites mediating this action have not been identified. We used morphine as a discriminative stimulus in a taste aversion paradigm to elucidate the neural basis of morphine's cueing properties. Rats were injected subcutaneously with 5 mg/kg morphine 15 min prior to the presentation of a 0.1% saccharin solution. After 20 min of exposure to the flavor, lithium chloride (130 mg/kg, IP) was injected. On alternate days, an injection of 0.9% physiological saline both preceded and followed the presentation of saccharin. Animals learned to consume significantly less saccharin after morphine than after saline injections. Unilateral guide cannulae were then implanted into brain areas containing relatively high densities of opiate binding sites, comprising the medial prefrontal cortex, the nucleus accumbens, the anterior dorsolateral striatum, the medial thalamus, the basolateral amygdaloid nucleus, the dorsal hippocampus, the caudal periaqueductal grey and the parabrachial nucleus. Generalization to central routes of administration was then evaluated by microinjecting morphine (2.5, 5, 10 and 20 micrograms) into these brain areas. Dose-dependent decreases in saccharin consumption similar to those of systemic morphine were produced by the administration of morphine into the parabrachial nucleus and the nucleus accumbens. Control data showed that only in the parabrachial nucleus could these effects be attributed to the cueing properties of morphine; in the nucleus accumbens, morphine administration induced unconditioned decreases in saccharin consumption. In the remaining brain areas, morphine generalized to the systemic saline condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Jaeger
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TV
Department of Anatomy and Cell Biology, University of Toronto, Ontario, Canada.
van der Kooy
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D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000502:physiology; D011149:Pons / Q000033:anatomy & histology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012439:Saccharin / Q000494:pharmacology
D009020:Morphine; D012439:Saccharin