Dopaminergic and noradrenergic inhibition of hypothalamic self-stimulation: differentiation of reward and performance effects.
Dopaminergic and noradrenergic inhibition of lateral hypothalamic self-stimulation was investigated in a new signalled, discrete-trials shuttle-box paradigm. The differential inhibitory effects of drugs and stimulation frequency reductions within small blocks of trials differentiate reward inhibition from a variety of performance deficits. They further differentiate among the deficits produced by fatigue, sedation, dyskinesias, akinesia and sensory disruption. Pimozide's selective inhibition of the first response within each block of trials shows that its inhibition of self-stimulation is not due to either an inhibition of reward or to a general performance deficit. Instead, it suggests that pimozide specifically inhibits the initiation of motor responding. Pimozide-induced akinesia appears to be partly reversible by hypothalamic stimulation. Thus the pimozide data do not support a role for dopamine in mediating brain-stimulation reward. Since the inhibitory effects of clonidine were very similar to those of pimozide, it is suggested that clonidine also produces a stimulation-reversible akinesia. Thus the clonidine data do not support a role for noradrenaline in mediating brain-stimulation reward. LU 5-003, which selectively inhibits the presynaptic reuptake of noradrenaline, inhibited self-stimulation in almost exactly the same way as did reducing reward by reducing stimulation frequency. These data do support a primary role for noradrenaline in mediating brain-stimulation reward. However, it is suggested that LU 5-003 inhibits self-stimulation, not by inhibiting reward, but by enhancing reward and making the electrical stimulation superfluous.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004567:Electrodes, Implanted; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012201:Reward; D012653:Self Stimulation / Q000502:physiology*; D013876:Thiophenes / Q000494:pharmacology
D013876:Thiophenes; D010868:Pimozide; C001750:talsupram; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine