Is the release of noradrenaline necessary for self-stimulation of the brain?
The hypothesis that a quantity of noradrenaline released contingently on every response made to obtain brain stimulation mediates the reward produced by the stimulation was tested. An alternative hypothesis is that reward is mediated by a different system, but that a steady activation of post-synaptic receptors by noradrenaline is necessary for normal behavior. The synthesis of noradrenaline was inhibited by disulfiran, and when lateral hypothalamic self-stimulation in the rat had ceased, alpha-adrenergic stimulants were injected intraventricularly (IC) or intraperitoneally (IP). The directly acting receptor stimulants oxymetazoline (0.9-250 mug IC), naphazoline (20-250 mug IC), and clonidine (0.75-3 mug IC, 0.037-3 mg/kg IP) did not restore self-stimulation, but the indirectly acting stimulants amphetamine (2 mg/kg IP), methylphenidate (3 mg/kg IP) and phenylephrine (15 mug IC) did not restore self-stimulation. In Experiments 2 and 3, in which either the functional noradrenaline pool was depleted with disulfiram and amphetamine, or the reserve noradrenaline pool was depleted with reserpine, the action of phenylephrine in restoring self-stimulation was shown to be indirect, probably by mobilizing a reserve pool of noradrenaline. Because only indirectly acting noradrenergic stimulants which facilitate the release of noradrenaline restores self-stimulation, it is concluded that noradrenaline must be released contingent on every response for self-stimulation to occur. Whether this released noradrenaline mediates the reward or has some other function associated with bar-pressing behavior remains to be shown.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009278:Naphazoline / Q000494:pharmacology; D009411:Nerve Endings / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000502:physiology; D010109:Oxymetazoline / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D012653:Self Stimulation
D011955:Receptors, Drug; D010656:Phenylephrine; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D007980:Levodopa; D001545:Benserazide; D012110:Reserpine; D010109:Oxymetazoline; D000661:Amphetamine; D009278:Naphazoline; D003000:Clonidine; D004221:Disulfiram; D009638:Norepinephrine