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Intracranial reward after Lilly 110140 (fluoxetine HCl): Evidence for an inhibitory role for serotonin

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Abstract

The 5-hydroxytryptamine (5-HT, serotonin) specific presynaptic reuptake inhibitor Lilly 110140 (fluoxetine hydrochloride) was injected systemically in rats trained to bar-press for rewarding stimulation to the caudal portion ofthe medial forebrain bundle. Rates of self stimulation were reduced in proportion to drug dosage, and these reductions were partially reversible by methysergide. These findings are consistent with previous reports suggesting an inhibitory role for 5-HT in self stimulation.

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References

  • Belluzzi, J. D., Ritter, S., Wise, C. D., Stein, L.: Substantia nigra self stimulation: Dependence upon noradrenergic reward pathways. Behav. Biol. 13, 103–111 (1975)

    Google Scholar 

  • Black, W. C., Cooper, B. R.: Reduction of electrically rewarded behavior by interference with monamine synthesis. Physiol. Behav. 5, 1405–1409 (1970)

    Google Scholar 

  • Bose, S., Bailey, P. T., Thoa, N. B., Pradhan, S. N.: Effects of 5-hydroxytryptophane on self stimulation in rats. Psychopharmacologia (Berl.) 36, 255–262 (1974)

    Google Scholar 

  • Blum, K., Geller, I.: Facilitation of brain stimulation with parachlorophenylalanine. Fed. Proc. 28, 794 (1969)

    Google Scholar 

  • Broekkamp, C. L. E., van Rossum, J. M.: Effects of apomorphine on self stimulation behavior. Psychopharmacologia (Berl.) 34, 71–80 (1974)

    Google Scholar 

  • Clavier, R. M., Routtenberg, A.: Ascending monoamine-containing fiber pathways related to intracranial self stimulation: histochemical fluorescence study. Brain Res. 72, 25–40 (1974)

    Google Scholar 

  • Clineschmidt, B. V., McGuffin, J. C., Werner, A. B.: Role of monoamines in the anorexigenic actions of fenfluramine, amphetamine, and p-chloromethamphetamine. Europ. J. Pharmacol. 27, 313–323 (1974)

    Google Scholar 

  • Cook, L., Sepinwall, J.: Behavioral analysis of the effects and mechanisms of action of benzodiazepines. In: Advances in biochemical psychopharmacology, Vol. 14 E. Costa and P. Greengard, eds. New York: Raven Press 1975

    Google Scholar 

  • Cooper, B. R., Black, W. C., Paolina, R. M.: Decreased septalforebrain and lateral hypothalamic reward after α-methyl paratyrosine. Physiol. Behav. 6, 425–429 (1971)

    Google Scholar 

  • Crow, T. J.: A map of the rat mesencephalon for electrical self stimulation. Brain Res. 36, 265–273 (1972a)

    Google Scholar 

  • Crow, T. J.: Catecholamine containing neurons and electrical self stimulation: I. A review of some data. Psychol. Med. 2, 414–421 (1972b)

    Google Scholar 

  • Dixon, W. J., Massey, F. J.: Introduction to statistical analysis, 3rd ed. New York: McGraw-Hill 1969

    Google Scholar 

  • Douglas, W. W.: Histamine and antihistamines; 5-hydroxytryptamine and antagonists. In: The pharmacological basis of therapeutics, L. Goodman and A. Gilman, eds., 5th ed., pp. 596–630. New York: MacMillan 1975

    Google Scholar 

  • Fuller, R. W., Perry, K. W.: Inability of an inhibitor of amine uptake (Lilly 110140) to block depletion of brain 5-hydroxytryptamine by L-Dopa. J. Pharm. Pharmacol. 27, 618–619 (1975a)

    Google Scholar 

  • Fuller, R. W., Perry, K. W., Molloy, B. B.: Effect of an uptake inhibitor on serotonin metabolism in the rat brain: Studies with 3-(-p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine (Lilly 110140). Life Sci. 15, 1161–1171 (1974a)

    Google Scholar 

  • Fuller, R. W., Perry, K. W., Molloy, B. B.: Effect of 3-(-p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine on the depletion of brain serotonin by 4-chloroamphetamine. J. Pharmacol. exp. Ther. 193, 796–803 (1975b)

    Google Scholar 

  • Fuller, R. W., Perry, K. W., Molloy, B. B.: Reversible and irreversible phase of serotonin depletion by 4-chloroamphetamine. Europ. J. Pharmacol. 33, 119–124 (1975c)

    Google Scholar 

  • Fuller, R. W., Perry, K. W., Snoddy, H. D., Molloy, B. B.: Comparison of the specificity of 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine as amine uptake inhibitors in mice. Europ. J. Pharmacol. 28, 233–236 (1974b)

    Google Scholar 

  • Gibson, S. E., McGeer, E. G., McGeer, P. L.: Effect of selective inhibitors of tyrosine and tryptophan hydroxylases on self stimulation in the rat. Exp. Neurol. 27, 283–290 (1970)

    Google Scholar 

  • Haigler, H. J., Aghajanian, G. R.: Peripheral serotonin antagonists: Failure to antagonize serotonin in brain areas receiving a prominent serotonin input. J. Neur. Trans. 35, 257–273 (1974)

    Google Scholar 

  • Koe, B. K., Weissman, A.: P-chlorophenylalanine: A specific depletor of brain serotonin. J. Pharmacol. exp. Ther. 154, 499–561 (1966)

    Google Scholar 

  • Konig, J. F. R., Klippel, R. A.: The rat brain—A stereotaxic atlas of the forebrain and lower parts of the brain stem. New York: Williams and Wilkins 1963

    Google Scholar 

  • Lorens, S.: Effect of lesions of the raphe system on self stimulation in the rat. Physiol. Behav. 7, 815–818 (1971)

    Google Scholar 

  • Luna, L. G.: Manual of histological staining methods of the armed forces Institute of Pathology. New York: McGraw-Hill 1960

    Google Scholar 

  • Margules, D. L.: Noradrenergic rather than serotonergic basis of reward in the dorsal tegmentum. J. comp. physiol. Psychol. 67, 32–35 (1969)

    Google Scholar 

  • Miliaressis, E., Bouchard, A., Jacobowitz, D.: Strong positive reward in the median Raphe, specific inhibition by para chlorophenylalanine. Brain Res. 98, 194–199 (1975)

    Google Scholar 

  • Miliaressis, E., Jacobowitz, D.: Hyperthermia following self-stimulation of the median Raphe. Pharm. Biochem. Behav. 4, 477–479 (1976)

    Google Scholar 

  • Phillips, A. G., Fibiger, H. C.: Dopaminergic and noradrenergic substrates of positive reinforcement: differential effects of d-and l-amphetamine. Science 179, 575–576 (1973)

    Google Scholar 

  • Phillips, K. C., Wray, S. E.: Failure of anti-serotonergic agents to modify levallorphan induced stereotypy in rats. Psychopharmacologia (Berl.) 41, 263–265 (1975)

    Google Scholar 

  • Poschel, B. P. H., Ninteman, F. W.: Norepinephrine: a possible excitatory neurohormone of the reward system. Life Sci. 2, 782–788 (1963)

    Google Scholar 

  • Poschel, B. P. H., Ninteman, F. W.: Hypothalamic self stimulation: its suppression by blockade of norepinephrine biosynthesis and reinstatement by methamphetamine. Life Sci. 5, 11–16 (1966)

    Google Scholar 

  • Poschel, B. P. H., Ninteman, F. W.: Excitatory effects of 5-HTP on intracranial self stimulation following MAO blockade. Life Sci. 7, 317–323 (1968)

    Google Scholar 

  • Poschel, B. P. H., Ninteman, F. W.: Intracranial reward and the forebrain's serotonergic mechanism: studies employing parachlorophenylalanine and para-chloroamphetamine. Physiol. Behav. 7, 39–46 (1971)

    Google Scholar 

  • Poschel, B. P. H., Ninteman, F. W., McLean, J. R., Potoczah, D.: Intracranial reward after 5, 6, dihydroxytryptamine: Further evidence for serotonin's inhibitory role. Life Sci. 15, 1515–1522 (1975)

    Google Scholar 

  • Ritter, S., Stein, L.: Self stimulation of the noradrenergic cell group (A6) in locus coeruleus of rats. J. comp. physiol. Psychol. 85, 443–452 (1973)

    Google Scholar 

  • Ritter, S., Stein, L.: Self stimulation in the mesencephalic trajectory of the ventral noradrenergic bundle. Brain Res. 81, 145–157 (1974)

    Google Scholar 

  • Roll, S. K.: Intracranial self stimulation and wakefulness, effects of manipulating ambient brain catecholamines. Science 168, 1370–1372 (1970)

    Google Scholar 

  • St-Laurent, J., Leclerc, R. R., Mirchell, M. L., Milliaressis, T. E.: Effects of apomorphine on self stimulation. Pharmacol. Biochem. Behav. 1, 581 (1973)

    Google Scholar 

  • Stark, P., Fuller, R. W., Hartley, L. W., Schaffer, R. J., Tuch, J. A.: Dissociation of the effects of p-chlorophenylalanine on self stimulation. Life Sci. 9, 41–48 (1970)

    Google Scholar 

  • Stein, L.: Effects and interactions of imipramine, chlorpromazine, reserpine and amphetamine on self stimulation: Possible neurophysiological basis of depression. In: Recent advances in biological psychiatry, J. Wortis, ed., pp. 288–308. New York: Plenum 1962

    Google Scholar 

  • Stein, L.: Chemistry of reward and punishment. In: Psychopharmacology: A review of Progress 1957–1967. D. H. Efron, ed., p. 105. Washington: U. S. Government Printing Office 1968

    Google Scholar 

  • Stinus, L., Thierry, A. M.: Self stimulation and catecholamines. II. Blockade of self stimulation by treatment with alpha-methylparatyrosine and the reinstatement by catecholamine precursor administration. Brain Res. 64, 189 (1973)

    Google Scholar 

  • Ungerstedt, U.: Stereotaxic mapping of the monoamine pathways in rat brain. Acta physiol. scand., Suppl. 367, 1–48 (1971)

    Google Scholar 

  • Wauquier, A., Niemegeers, C. J. E.: Intracranial self stimulation in rats as a function of various stimulus parameters. II. Influence of haloperidol, pimozide and pepamperone on medial forebrain bundle stimulation with monopolar electrodes. Psychopharmacologia (Berl.) 27, 191–202 (1972)

    Google Scholar 

  • Wise, C. D., Berger, B. D., Stein, L.: Evidence of α-noradrenergic reward receptors and serotonergic punishment receptors in the rat brain. Biol. Psychiat. 6, 3–22 (1973)

    Google Scholar 

  • Wong, D. T., Bymaster, F. R., Horing, J. S., Molloy, B. B.: A new selective inhibitor for uptake of serotonin into synaptosomes of rat brain (3-p-trifluoromethylphenoxy)-n-methyl-3-phenylpropylamine. J. Pharmacol. exp. Ther. 193, 804–811 (1975)

    Google Scholar 

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Katz, R.J., Carroll, B.J. Intracranial reward after Lilly 110140 (fluoxetine HCl): Evidence for an inhibitory role for serotonin. Psychopharmacology 51, 189–193 (1977). https://doi.org/10.1007/BF00431739

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