Skip to main content
SpringerLink
Log in

Methiothepin reduces glucose utilization in forebrain regions of awake rats

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-d-glucose method, in 92 discrete brain regions of awake rats, at 1, 2, 3, or 4 h after administration of the serotonergic antagonist methiothepin 0.1 mg/kg IP. The drug produced a cataleptic behavior that peaked in intensity at 3 h after its administration. LCGU declined significantly in 35% of the 92 regions at one or more time points after methiothepin administration. No area of increased metabolism was found. The time-course of the decline in LCGU closely paralleled the intensity of catalepsy; the peak effect was at 3 h, when LCGU was significantly reduced in 32% of the regions examined (mean decline for all regions was 15%). Metabolic depression after methiothepin was most notable in the forebrain, where LCGU declined in many regions of the cerebral cortex, basal ganglia, and thalamus. Most of the regions affected by methiothepin possess a substantial number of serotonin receptors, although LCGU was also reduced in a few regions not primarily involved in serotonergic neurotransmission.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aghajanian GK (1981) The modulatory role of serotonin at multiple receptors in brain. In: Jacobs LB, Gelperin A (ed) Serotonin neurotransmission and behavior. MIT Press, Cambridge, MA, pp 156–185

    Google Scholar 

  • Balsara JJ, Jadhav JH, Chandorkar AG (1979) Effect of drugs influencing central serotonergic mechanisms on haloperidol-induced catalepsy. Psychopharmacology 62:67–69

    Google Scholar 

  • Baumann PA, Waldmeier PC (1981) Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn-Schmiedeberg's Arch Pharmacol 317:36–43

    Google Scholar 

  • Biegon A, Rainbow TC, McEwen BS (1982) Quantitative autoradiography of serotonin receptors in the rat brain. Brain Res 242:197–204

    Google Scholar 

  • Blackshear MA, Steranka LR, Sanders-Bush E (1981) Multiple serotonin receptors: regional distribution and effect of raphe lesions. Eur J Pharmacol 76:325–334

    Google Scholar 

  • Cerrito F, Raiteri M (1980) Presynaptic autoreceptors control serotonin release from central nerve endings. Pharmacol Res Commun 12:593–597

    Google Scholar 

  • Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of anti-schizophrenic drugs. Science 192:481–483

    Google Scholar 

  • Dahlstrom A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. Acta Physiol Scand [Suppl] 232:1–55

    Google Scholar 

  • Dunnett CW (1964) New tables for multiple comparisons with a control. Biometrics 20:482–491

    Google Scholar 

  • Gothert M (1982) Modulation of serotonin release in the brain via presynaptic receptors. TIPS 4:437–440

    Google Scholar 

  • Gothert M, Schlicker E (1983) Autoreceptor-mediated inhibition of 3H-5-hydroxytryptamine release from rat brain cortex slices by analogues of 5-hydroxytryptamine. Life Sci 32:1183–1191

    Google Scholar 

  • Green AR, Hall JE, Rees AR (1981) A behavioral and biochemical study in rats of 5-hydroxytryptamine receptor agonists and antagonists, with observations on structure-activity requirements for the agonists. Br J Pharmacol 73:703–719

    Google Scholar 

  • Hodes JE, Soncrant TT, Larson DM, Carlson SG, Rapoport SI (1985) Changes in cerebral glucose utilization induced by phenobarbital in the rat. Anesthesiology 63:633–639

    Google Scholar 

  • Jacobs BL (1976) An animal behavior model for studying central serotonergic synapses. Life Sci 19:777–786

    Google Scholar 

  • Konig JFR, Klippel RA (1967) The rat brain — a stereotaxic atlas of the forebrain and lower parts of the brain stem. Krieger, Huntington, New York

    Google Scholar 

  • Lloyd KG, Bartolini G (1974) The effect of methiothepin on cerebral monoamine neurons. Adv Biochem Psychopharmacol 10:305–309

    Google Scholar 

  • Martin LL, Sanders-Bush E (1982) Comparison of the pharmacological characteristics of 5-HT1 and 5-HT2 binding sites with those of serotonin autoreceptors which modulate serotonin release. Naunyn-Schmiedeberg's Arch Pharmacol 321:165–170

    Google Scholar 

  • Matthews WD, Smith CD (1980) Pharmacological profile of a model for central serotonin receptor activation. Life Sci 26:1397–1403

    Google Scholar 

  • McNamara D, Larson DM, Soncrant TT, Rapoport SI (1985) Effects of nicotine on regional cerebral glucose metabolism in the rat. Trans Am Soc Neurochem 16:49

    Google Scholar 

  • Miller RG (1981) Simultaneous statistical inference, McGraw Hill, New York, pp 76–81

    Google Scholar 

  • Monachon MA, Burkard WP, Jalfre M, Haefely W (1972) Blockade of central 5-hydroxytryptamine receptors by methiothepin. Naunyn-Schmiedeberg's Arch Pharmacol 274:192–197

    Google Scholar 

  • Moore RY (1981) The anatomy of central serotonin neuron system in the rat brain. In: Jacobs LB, Gelperin A (ed) Serotonin neurotransmission and behavior, MIT Press, Cambridge, MA, pp 35–71

    Google Scholar 

  • Nelson DL (1982) Central serotonergic receptors: evidence for heterogeneity and characterization by ligand-binding. Neurosci Biobehav 6:499–502

    Google Scholar 

  • Nelson DL, Herbet A, Pichat L, Glowinski J, Hanon M (1979) In vitro and in vivo disposition of 3H-methiothepin in brain tissues. Naunyn-Schmiedeberg's Arch Pharmacol 310:25–33

    Google Scholar 

  • Palacios JM, Probst A, Cortes R (1983) The distribution of serotonin receptors in the human brain: high density of [3H]LSD bining sites in the raphe nuclei of the brainstem. Brain Res 274:150–155

    Google Scholar 

  • Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346:205–230

    Google Scholar 

  • Pazos A, Cortes R, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors. Brain Res 346:231–249

    Google Scholar 

  • Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic, New York

    Google Scholar 

  • Peroutka SJ (1986) Pharmacological differentiation and characterization of 5-HT1A, 5-HT1B, and 5-HT1C binding sites in rat frontal cortex. J Neurochem 47:529–540

    Google Scholar 

  • Peroutka SJ, Snyder SH (1983) Multiple serotonin receptors and their physiological significance. Fed Proc 42:213–217

    Google Scholar 

  • Pettibone DJ, Pflueger BA (1984) Effects of methiothepin and lysergic acid diethylamide on serotonin release in vitro and serotonin synthesis in vivo: possible relation to serotonin autoreceptor function. J Neurochem 43:83–90

    Google Scholar 

  • Pizzolato G, Soncrant TT, Rapoport SI (1984) Halperidol and cerebral metabolism in the conscious rat: relation to pharmacokinetics. J Neurochem 43:724–732

    Google Scholar 

  • Pizzolato G, Soncrant TT, Rapoport SI (1985) Time-course and regional distribution of the metabolic effects of bromocriptine in the rat brain. Brain Res 341:303–312

    Google Scholar 

  • Pizzolato G, Soncrant TT, Larson DM, Rapoport SI (1987) Stimulatory effect of the D2 antagonist sulpiride on glucose utilization in dopaminergic regions of rat brain. J Neurochem 49:631–638

    Google Scholar 

  • Protiva M (1977) Metitepine. Drugs of the future, vol II, no 4, pp 250–267

    Google Scholar 

  • Ricchieri GL, Soncrant TT, Holloway HW, Rapoport SI (1985a) The effects of methiothepin on local cerebral glucose metabolism in the awake rat. J Neurochem [Suppl] 44:168

    Google Scholar 

  • Ricchieri GL, Soncrant TT, Rapoport SI (1985b) The effects of serotonergic agents quipazine and methiothepin on local cerebral glucose utilization in the rat. Soc Neurosci Abstr 11:1261

    Google Scholar 

  • Segawa T, Uehara M (1982) Effect of methiothepin on imipramineor mianserin-induced subsensitivity of serotonergic receptors. Life Sci 30:809–812

    Google Scholar 

  • Sloviter RS, Drust EG, Connor JD (1978) Specificity of a rat behavioural model for serotonin receptor activation. J Pharmacol Exp Ther 206:339–347

    Google Scholar 

  • Sokoloff L (1977) Relation between physiological function and energy metabolism in the central nervous system. J Neurochem 29:13–26

    Google Scholar 

  • Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916

    CAS  PubMed  Google Scholar 

  • Soncrant TT, Holloway HW, Carlson S, Rapoport SI (1983) Local cerebral glucose utilization (LCGU) in rats is unaffected by immobilization stress of experimental preparation. Soc Neurosci Abstr 9:972

    Google Scholar 

  • Soncrant TT, Holloway HW, Rapoport SI (1985) Arecoline-induced elevations of regional cerebral metabolism in the conscious rat. Brain Res 347:205–216

    Google Scholar 

  • Soncrant TT, Pizzolato G, Battistin L (1986) The use of drugs as probes of cerebral function. In: Battistin L, Gerstenbrand F (eds) PET and NMR: New perspectives in neuroimaging and in clinical neurochemistry. Liss, New York, pp 131–149

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Building 10, Room 6C103, 20892, Bethesda, MD, USA

    G. L. Ricchieri, T. T. Soncrant, H. W. Holloway & S. I. Rapoport

Authors
  1. G. L. Ricchieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. T. Soncrant
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. W. Holloway
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. I. Rapoport
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ricchieri, G.L., Soncrant, T.T., Holloway, H.W. et al. Methiothepin reduces glucose utilization in forebrain regions of awake rats. Psychopharmacology 93, 449–456 (1987). https://doi.org/10.1007/BF00207234

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00207234

Key words

Search

Navigation