Skip to main content
SpringerLink
Log in

Striatal regulation of morphine-induced hyperphagia: an anatomical mapping study

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

Abstract

Both systemic and intracranial administration of morphine can result in spontaneous feeding in nondeprived rats. The present investigation was conducted to examine the involvement of the striatum in this phenomenon. Morphine sulfate (0, 0.5, 1.0, 5.0, 10.0, and 20.0 µg/0.5 µl) was microinjected into five discrete striatal subregions in non-deprived rats: the nucleus accumbens, the ventromedial striatum, the ventrolateral striatum, the anterior dorsal striatum, and the posterior dorsal striatum. Feeding, drinking, locomotion, rearing, and food intake were measured over 4 h after infusion. Results indicate that the striatum is a heterogeneous structure with regard to the regulation of opiate-induced feeding behavior and locomotor activity. Morphine infusion into anteroventromedial regions including the nucleus accumbens resulted in a marked hyperphagia that was generally delayed in onset; much smaller increases or no change in feeding occurred after administration into more dorsal, lateral and posterior areas. It is hypothesized that there may exist within the striatum an anatomical gradient that is most sensitive to opiate-induced feeding within the anteroventromedial sector. Since this area has extensive connections with other brain sites sensitive to opiate-induced feeding, it may be a critical part of an opiatergic feeding system within the brain. In addition, a possible role for the anteroventromedial striatum in compulsive feeding and bulimia is discussed.

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

  • Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. TINS 13:266–271

    PubMed  Google Scholar 

  • Bakshi VP, Kelley AE (1991a) Dopaminergic regulation of feeding behavior: I. Differential effects of haloperidol microinfusion into three striatal subregions. Psychobiology 19:223–232

    Google Scholar 

  • Bakshi VP, Kelley AE (1991b) Dopaminergic regulation of feeding behavior: II. Differential effects of amphetamine microinfusion into three striatal subregions. Psychobiology 19:233–242

    Google Scholar 

  • Bakshi VP, Kelley AE, Fleming SM (1992) Repeated morphine in nucleus accumbens: conditioning and sensitization of feeding. Soc Neurosci Abstr 18:743

    Google Scholar 

  • Baxter LR, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE (1987) Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Arch Gen Psychiatry 44:211–218

    PubMed  Google Scholar 

  • Cador M, Kelley AE, Le Moal M, Stinus L (1986) Ventral tegmental area infusion of substance P, neurotensin, and enkephalin: differential effects on feeding behavior. Neuroscience 18:659–669

    Article  PubMed  Google Scholar 

  • Cunningham ST, Kelley AE (1992) Opiate infusion into nucleus accumbens: Contrasting effects on motor activity and responding for conditioned reward. Brain Res (in press)

  • Daugé V, Rossignol P, Roques BP (1988) Comparison of the behavioral effects induced by administration in rat nucleus accumbens or nucleus caudatus of selectiveμ andδ opioid peptides or kelatorphan, an inhibitor of enkephalin-degrading enzymes. Psychopharmacology 96:343–352

    Google Scholar 

  • Evans KR, Vaccarino FJ (1990) Amphetamine- and morphine-induced feeding: evidence for involvement of reward mechanisms. Neurosci Biobehav Rev 14:9–22

    Article  PubMed  Google Scholar 

  • Gosnell BA, Morley JE, Levine AS (1984) Lesions of the globus pallidus and striatum attenuate ketocyclazocine-induced feeding. Physiol Behav 33:349–355

    Article  PubMed  Google Scholar 

  • Gosnell BA, Morley JE, Levine AS (1986) Opioid-induced feeding: Localization of sensitive brain sites. Brain Res 369:177–184

    Article  PubMed  Google Scholar 

  • Grandison L, Guidotti A (1977) Stimulation of food intake by muscimol and beta endorphin. Neuropharmacology 16:533–536

    Article  PubMed  Google Scholar 

  • Hamilton ME, Bozarth MA (1988) Feeding elicited by dynorphin (1–13) microinjections into the ventral tegmental area in rats. Life Sci 43:941–946

    Article  PubMed  Google Scholar 

  • Havemann U, Kuschinsky K (1985) Locomotor activity of rats after injection of various opioids into the nucleus accumbens and the septum mediale. Naunyn-Schmiedeberg's Arch Pharmacol 331:175–180

    Article  Google Scholar 

  • Heimer L, Alheid GF, Zaborsky L (1985) Basal ganglia. In: Paxinos G (ed) The rat nervous system. Academic Press, New York, pp 37–86

    Google Scholar 

  • Hoebel BG (1984) Neurotransmitters in the control of feeding and its rewards: Monoamines, opiates, and brain-gut peptides. In: Stunkard AJ, Stellar E (eds) Eating and its disorders. Raven Press, New York, pp 15–38

    Google Scholar 

  • Holtzman SG (1974) Behavioral effects of separate and combined administration of naloxone andd-amphetamine. J Pharmacol Exp Ther 189:51–60

    PubMed  Google Scholar 

  • Hughes J (1975) Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Res 88:295–308

    Article  PubMed  Google Scholar 

  • Kalivas PW, Widerlov E, Stanley D, Breese G, Prange AJ (1983) Enkephalin action on the mesolimbic system: a dopamine dependent and a dopamine independent increase in locomotor activity. J Pharmacol Exp Ther 227:229–237

    PubMed  Google Scholar 

  • Kelley AE, Delfs JM (1991) Dopamine and conditioned reinforcement. I. Differential effects of amphetamine microinjections into striatal subregions. Psychopharmacology 103:187–196

    PubMed  Google Scholar 

  • Kelley AE, Lang CG, Gauthier AM (1988) Induction of oral stereotypy following amphetamine microinjection into a discrete subregion of the striatum. Psychopharmacology 95:556–559

    Google Scholar 

  • Kelley AE, Bakshi VP, Delfs JM, Lang CG (1989a) Cholinergic stimulation of the ventrolateral striatum elicits mouth movements in rats: pharmacological and regional specificity. Psychopharmacology 99:542–547

    Article  PubMed  Google Scholar 

  • Kelley AE, Gauthier AM, Lang CG (1989b) Amphetamine microinjections into distinct striatal subregions cause dissociable effects on motor and ingestive behavior. Behav Brain Res 35:27–39

    PubMed  Google Scholar 

  • Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242:715–723

    PubMed  Google Scholar 

  • Kunihara M, Kanbayashi M, Ohshima T (1983) Opposite effects of morphine on feeding and drinking in rats relative to administration time. Jpn J Pharmacol 33:829–835

    PubMed  Google Scholar 

  • Leibowitz SF (1985) Brain neurotransmitters and appetite regulation. Psychopharmacol Bull 21:412–417

    PubMed  Google Scholar 

  • Leshem M (1988) Morphine induces delayed anorexia in rats. Psychopharmacology 94:254–258

    Article  PubMed  Google Scholar 

  • Levine AS, Billington CJ (1989) Opioids: are they regulators of feeding? In: Schneider LH, Cooper SJ, Halmi KA (eds) The psychobiology of human eating disorders: preclinical and clinical perspectives. Annals of the New York Academy of Sciences, New York, 575:209–220

    Google Scholar 

  • Levine AS, Morley JE, Gosnell BA, Billington CJ, Bartness TJ (1985) Opioids and consummatory behavior. Brain Res Bull 14:663–672

    Article  PubMed  Google Scholar 

  • Majeed NH, Przewlocka B, Wedzony K, Przewlocki R (1986) Stimulation of food intake following opioid microinjection into the nucleus accumbens septi in rats. Peptides 7:711–716

    Article  PubMed  Google Scholar 

  • Mansour A, Kachaturian H, Lewis ME, Akil H, Watson SJ (1987) Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain. J Neurosci 7:2445–2464

    PubMed  Google Scholar 

  • McGeorge AJ, Faull RLM (1989) The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience 29:503–537

    Article  PubMed  Google Scholar 

  • McLean S. Hoebel BG (1982) Opiate and norepinephrine-induced feeding from the paraventricular nucleus of the hypothalamus are dissociable. Life Sci 31:2379–2382

    Article  PubMed  Google Scholar 

  • McLean S, Hoebel BG (1983) Feeding induced by opiates injected into the paraventricular hypothalamus. Peptides 4:287–292

    Article  PubMed  Google Scholar 

  • Morley JE, Levine AS, Yim GK, Lowy MT (1983) Opioid modulation of appetite. Neurosci Biobehav Rev 7:281–305

    Article  PubMed  Google Scholar 

  • Mucha RF, Iversen SD (1986) Increased food intake after opioid microinjections into nucleus accumbens and ventral tegmental area of rat. Brain Res 397:214–224

    Article  PubMed  Google Scholar 

  • Pellegrino LJ, Cushman AJ (1967) A stereotaxic atlas of the rat brain. Appleton-Century-Crofts, New York

    Google Scholar 

  • Pert A, Sivit C (1977) Neuroanatomical focus for morphine and enkephalin-induced hypermotility. Nature 265:645–646

    Article  PubMed  Google Scholar 

  • Pert CB, Snyder SH (1973) Opiate receptor: demonstration in nervous tissue. Science 179:1011–1014

    PubMed  Google Scholar 

  • Pitman RK (1989) Animal models of compulsive behavior. Biol Psychiatry 26:189–198

    Article  PubMed  Google Scholar 

  • Reid LD (1985) Endogenous opioid peptides and regulation of drinking and feeding. Am J Clin Nutr 42:1099–1132

    PubMed  Google Scholar 

  • Sanger DJ (1981) Endorphinergic mechanisms in the control of food and water intake. Appetite 2:193–208

    PubMed  Google Scholar 

  • Shor-Posner G, Azar AP, Filart R, Tempel D, Leibowitz SF (1986) Morphine-stimulated feeding: analysis of macronutrient selection and paraventricular nucleus lesions. Pharmacol Biochem Behav 24:931–939

    Article  PubMed  Google Scholar 

  • Simon EJ, Hiller JM, Edelmann I (1973) Stereospecific binding of the potent narcotic analgesic3H-etorphin to rat brain homogenate. Proc Natl Acad Sci USA 70:1947–1949

    PubMed  Google Scholar 

  • Stanley BG, Lanthier D, Leibowitz SF (1989) Multiple brain sites sensitive to feeding stimulation by opioid agonists: a cannula mapping study. Pharmacol Biochem Behav 31:825–832

    Article  Google Scholar 

  • Tempel A, Zukin RS (1987) Neuroanatomical patterns of the mu, delta, and kappa opioid receptors of rat brain as determined by quantitative in vitro autoradiography. Proc Natl Acad Sci USA 84:4308–4312

    PubMed  Google Scholar 

  • Tepperman FS, Hirst M, Gowdey CW (1981a) Hypothalamic injection of morphine: feeding and temperature responses. Life Sci 28:2459–2467

    Article  PubMed  Google Scholar 

  • Tepperman FS, Hirst M, Gowdey CW (1981b) A probable role for norepinephrine in feeding after hypothalamic injection of morphine. Pharmacol Biochem Behav 15:555–558

    Article  PubMed  Google Scholar 

  • Tepperman FS, Hirst M (1983) Effect of intrahypothalamic injection of [d-Ala2,d-Leu5] enkephalin on feeding and temperature in the rat. Eur J Pharmacol 96:243–249

    Article  PubMed  Google Scholar 

  • Terenius L (1973) Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex. Acta Pharmacol Toxicol 32:317–320

    Google Scholar 

  • Terenius L, Wahlstrom A (1974) Inhibitors of narcotic receptor binding in brain extracts and cerebrospinal fluid. Acta Pharmacol Toxicol 35:55

    Google Scholar 

  • Wise RA (1989) Opiate reward: sites and substrates. Neurosci Biobehav Rev 13:129–133

    PubMed  Google Scholar 

  • Woods JS, Leibowitz SF (1985) Hypothalamic sites sensitive to morphine and naloxone: effects on feeding behavior. Pharmacol Biochem Behav 23:431–438

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Vaishali P. Bakshi

    Present address: Neuroscience Graduate Office, University of California at San Diego, Basic Science Building, 9600 Gilman Drive, 92093, La Jolla, CA, USA

Authors and Affiliations

  1. Department of Psychology, Northeastern University, 125 Nightingale Hall, 107 Forsyth Street, 02115, Boston, MA, USA

    Vaishali P. Bakshi & Ann E. Kelley

Authors
  1. Vaishali P. Bakshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ann E. Kelley
    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

Bakshi, V.P., Kelley, A.E. Striatal regulation of morphine-induced hyperphagia: an anatomical mapping study. Psychopharmacology 111, 207–214 (1993). https://doi.org/10.1007/BF02245525

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245525

Key words

Search

Navigation