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Evidence for selective inhibition of limbic forebrain dopamine synthesis by 8-OH-DPAT in the rat

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Regional dopamine synthesis in the rat striatum was estimated by measuring DOPA accumulation following inhibition of cerebral aromatic l-amino acid decarboxylase by means of NSD-1015, 100 mg kg−1 intraperitoneally. In animals treated with reserpine, 5 mg kg−1 subcutaneously −18 h, there was a statistically significant increase in DOPA accumulation in the nucleus accumbens, the ventro-medial neostriatum, the dorso-lateral neostriatum and in the posterior limb of the neostriatum. This increase in DOPA accumulation was antagonized dose-dependently in the nucleus accumbens and ventro-medial neostriatum, but not in the other two regions, by treatment with the 5-HT1A receptor agonist 8-OH-DPAT, 0.15–2.4 μmol kg−1, whereas the partial dopamine D2 receptor agonist (−)3-PPP, 2.5–10.0 μmol kg−1, or the full dopamine D2 receptor agonist quinpirole, 0.05–0.8 μmol kg−, antagonized the reserpine-induced increase in DOPA accumulation uniformly in all four regions of the striatum. The suppression of DOPA accumulation by 8-OH-DPAT in reserpine-treated animals, was completely antagonized by raclopride, 1 μmol kg−1, but not by (−)pindolol, 8 μmol kg−1. The accumulation of 5-HTP in all regions of the striatum as well as in the neocortex following decarboxylase inhibition and reserpine pretreatment, was also inhibited by 8-OH-DPAT, and this inhibition was unaffected by treatment with raclopride or (−)pindolol. It is concluded that 8-OH-DPAT, in addition to general effects on forebrain 5-hydroxytryptamine synthesis, selectively affects limbic forebrain dopamine synthesis. This latter effect is probably due to direct stimulation of dopamine autoreceptors, since it was obtained in reserpine-treated rats, and was completely antagonized by raclopride, but not (−)pindolol.

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Authors and Affiliations

  1. Department of Neuropharmacology, Astra Research Centre, S-151 85, Södertälje, Sweden

    Sven Ahlenius & Viveka Hillegaart

  2. Department of Bioanalysis, Astra Research Centre, S-151 85, Södertälje, Sweden

    Agneta Wijkström

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  1. Sven Ahlenius
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  2. Viveka Hillegaart
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Ahlenius, S., Hillegaart, V. & Wijkström, A. Evidence for selective inhibition of limbic forebrain dopamine synthesis by 8-OH-DPAT in the rat. Naunyn-Schmiedeberg's Arch Pharmacol 339, 551–556 (1989). https://doi.org/10.1007/BF00167260

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