Comparative involvement of dopamine and noradrenaline in rate-free self-stimulation in substantia nigra, lateral hypothalamus, and mesencephalic central gray
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- Liebman, J.M. & Butcher, L.L. Naunyn-Schmiedeberg's Arch. Pharmacol. (1974) 284: 167. doi:10.1007/BF00501121
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Previous research has shown that self-stimulation (SS) is found in substantia nigra (SN) and that SS in other loci is altered by drugs preferentially influencing dopaminergic neurotransmission. In the first part of this investigation the effects of pimozide (0.35 and 0.5 mg/kg), apomorphine (0.25, 0.5, 0.75 and 1.5 mg/kg), d-amphetamine (0.1, 0.25, and 1.0 mg/kg) and L-amphetamine (0.25, 1.0, and 2.5 mg/kg) on SS in lateral hypothalamus (HL) and SN were separately determined. To reduce possible confounding of drug effects on SS with non-specific changes in motor activation, a rate-free test of SS was employed. Pimozide (0.5 mg/kg) reduced SS more strongly in SN than in HL, confirming the existence of a dopaminergic substrate of SS in SN, but HL SS was also reduced by this drug. Low doses of apomorphine (0.25 and 0.5 mg/kg) elevated SS in HL while not influencing or slightly reducing SS in SN. Higher doses of apomorphine reduced SS in both regions. The enhancing effect of 0.1 mg/kg d-amphetamine on SS was greater in HL than in SN. However, d-amphetamine tended to increase SS more strongly than did L-amphetamine in SN as well as HL. It was concluded that HL SS may be mediated by both noradrenergic and dopaminergic substrates.
An investigation was also undertaken into the possibility of noradrenergic or dopaminergic mediation of SS in other brain regions. Self-stimulation in the dorsal raphé area of mesencephalic central gray matter was not increased by 0.1 or 0.25 mg/kg d-amphetamine and was elevated only at 1.0 mg/kg, a dose level well above that needed to elevate HL or SN SS. In this region, therefore, SS did not appear to have either a noradrenergic or a dopaminergic substrate.