Skip to main content
SpringerLink
Log in

Interactions of naloxone with morphine, amphetamine and phencyclidine on fixed interval responding for intracranial self-stimulation in rats

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

Abstract

Rats were implanted with stimulating electrodes aimed at the medial forebrain bundle-lateral hypothalamus (MFB-LH) and were trained to lever-press for brain self-stimulation on a fixed interval: 60 s schedule of reinforcement. The effects of graded doses of naloxone (0.1–30 mg/kg), morphine (0.3–5.6 mg/kg), naloxone plus morphine,d-amphetamine (0.03–1.0 mg/kg), naloxone plusd-amphetamine, phencyclidine (0.3–5.6 mg/kg), and naloxone plus phencyclidine were tested. Naloxone produced a significant decrease in rates at 30 mg/kg. Naloxone (0.1–1.0 mg/kg) plus morphine blocked the dose-dependent decrease produced by morphine alone. In contrast, naloxone (1.0–10 mg/kg) plusd-amphetamine attenuated the graded increase in response rates produced byd-amphetamine. Naloxone (1.0–10 mg/kg) plus phencyclidine did not reliably change the increase in response rates produced by phencyclidine alone. The use of the fixed interval schedule of brain self-stimulation to study these drug interactions is novel, and further demonstrates that the highly reinforcing aspects of brain stimulation, known to be influenced by dopamine, may also be modulated by the endogenous opiate system.

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

  • Adam-Carriere D, Merali Z, Stretch R (1978) Effects of morphine, naloxone,d,l-cyclazocine, andd-amphetamine on behaviour controlled by a schedule of interresponse time reinforcement. Can J Physiol Pharmacol 56:707–720

    Google Scholar 

  • Bain GT, Kornetsky C (1987) Naloxone attenuation of the effect of cocaine on rewarding brain simulation. Life Sci 40:1119–1125

    Google Scholar 

  • Balster RL, Chait LD (1978) The behavioral effects of phencyclidine in animals. In: Petersen RC, Stillman RC (eds) Phencyclidine (PCP) abuse: an appraisal. NIDA Res Monogr 21, DHEW, Washington, DC, pp 53–65

    Google Scholar 

  • Bozarth MA (1987) (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Brown S, Trowill JA (1970) Lever-pressing performance for brain stimulation on F-I and V-I schedules in a single-lever situation. Psychol Rep 26:699–706

    Google Scholar 

  • Carey RJ, Goodall EB (1973) A comparison of the effects of amphetamine on fixed interval performance maintained by electrical stimulation of the brain versus food reinforcement. Pharmacol Biochem Behav 1:237–239

    Google Scholar 

  • Castellani S, Giannini AJ, Adams PM (1982) Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat. Psychopharmacology 78:76–80

    Google Scholar 

  • Collier TJ, Routtenberg A (1984) Electrical self-stimulation of dentate gyrus granule cells. Behav Neural Biol 42:85–90

    Google Scholar 

  • Contreras PC, Contreras ML, O'Donohue TL, Lair CC (1988) Biochemical and behavioral effects of sigma and PCP ligands. Synapse 2:240–243

    Google Scholar 

  • Deutch AY, Tam S-Y, Freeman AS, Bowers MB Jr, Roth RH (1987) Mesolimbic and mesocortical dopamine activation induced by phencyclidine: contrasting pattern to striatal response. Eur J Pharmacol 134:257–264

    Google Scholar 

  • Engel J, Oreland L (1987) Brain reward systems and abuse. Raven Press, New York

    Google Scholar 

  • Esposito RU, Perry W, Kornetsky C (1980) Effects ofd-amphetamine and naloxone on brain stimulation reward. Psychopharmacology 69:187–191

    Google Scholar 

  • French ED (1988) Effects of acute and chronic administration of phencyclidine on the A10 dopaminergic mesolimbic system: electrophysiological and behavioral correlates. Neuropharmacology 27:791–798

    Google Scholar 

  • Glick SD, Rapaport G (1974) Tolerance to the facilitatory effect of morphine on self-stimulation of the medial forebrain bundle in rats. Res Comm Chem Pathol Pharmacol 9:647–652

    Google Scholar 

  • Greenshaw AJ, Sanger DJ, Blackman DE (1985) Effects ofd-amphetamine and of beta-phenylethylamine on fixed interval responding maintained by self-regulated lateral hypothalamic stimulation in rats. Pharmacol Biochem Behav 23:519–523

    Google Scholar 

  • Harris RA, Snell D (1980) Interactions between naltrexone and non-opiate drugs evaluated by schedule-controlled behavior. Neuropharmacology 19:1087–1093

    Google Scholar 

  • Hernandez L, Auerbach S, Hoebel BG (1988) Phencyclidine (PCP) injected in the nucleus accumbens increases extracellular dopamine and serotonin as measured by microdialysis Life Sci 42:1713–1723

    Google Scholar 

  • Holtzman SG (1976) Comparison of the effects of morphine, pentazocine, cyclazocine and amphetamine on intracranial self-stimulation in the rat. Psychopharmacologia 46:223–227

    Google Scholar 

  • Itemtani Y, Iwasaki T, Satoh T (1985) Effects of naloxone and chlordiazepoxide on lateral hypothalamic self-stimulation in rats. Physiol Behav 34:779–782

    Google Scholar 

  • Kornetsky C, Markowitz RA, Esposito RU (1981) Phencyclidine and naloxone: effects on sensitivity to aversive and rewarding stimulation in the rat. In: Domino EF (ed): PCP (phencyclidine): historical and current perspectives. NPP Books, Ann Arbor, Michigan, pp 321–330

    Google Scholar 

  • McMillan DE (1974) Effects of narcotics and narcotic antagonists on operant behavior. In: Braude MC, Harris LS, May EL, Smith JP, Villarreal JE (eds) Narcotic antagonists, vol 8. Advances in biochemical psychopharmacology. Raven Press, New York, pp 345–359

    Google Scholar 

  • Morse WH (1966) Intermittent reinforcement. In: Honig WK (ed) Operant behavior: areas of research and application. Appleton Century Crofts, New York, pp 52–108

    Google Scholar 

  • Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Plenum Press, New York

    Google Scholar 

  • Pert A, Hulsebus R (1975) Effect of morphine on intracranial self-stimulation behavior following brain amine depletion. Life Sci 17:19–20

    Google Scholar 

  • Reid LD (1987) Tests involving pressing for intracranial stimulation as an early procedure for screening likelihood of addiction of opioids and other drugs. In: Bozarth MJ (ed) Methods of assessing the reinforcing properties of abuse drugs. Springer, Berlin Heidelberg, New York, pp 391–420

    Google Scholar 

  • Reynolds GS (1968) A primer of operant conditioning. Scott, Foresman, Glenview, Illinois

    Google Scholar 

  • Schaefer GJ (1988) Opiate antagonists and rewarding brain stimulation. Neurosci Biobehav Rev 12:1–17

    Google Scholar 

  • Schaefer GJ, Bonsall RW, Michael RP (1982) An easily constructed biphasic constant-current stimulator for intracranial self-stimulation Physiol Behav 29:163–165

    Google Scholar 

  • Schaefer GJ, Michael RP (1981) Threshold differences for naloxone and naltrexone in the hypothalamus and midbrain using fixed ratio brain self-stimulation in rats. Psychopharmacology 74:17–22

    Google Scholar 

  • Schmauss C, Emrich HM (1985) Dopamine and the action of opiates: a reevaluation of the dopamine hypothesis of schizophrenia: with special consideration of the role of endogenous opioids in the pathogenesis of schizophrenia. Biol Psychiatry 20:1211–1231

    Google Scholar 

  • Shannon HE (1982) Pharmacological analysis of the phencyclidine-like discriminative stimulus properties of narcotic derivatives in rats. J Pharmacol Exp Ther 222:146–151

    Google Scholar 

  • Smith JE, Lane JD (1983) (eds) The neurobiology of opiate reward processes. Elsevier Biomedical Press, New York

    Google Scholar 

  • Stein L, Belluzzi JD (1978) Brain endorphins and the sense of well-being: a psychobiological hypothesis. In: Costa E, Trabucchi M (eds) The endorphins, vol 18. Advances in biochemical psychopharmacology. Raven Press, New York, pp 299–311

    Google Scholar 

  • Stellar JR, Stellar E (1985) The neurobiology of motivation and reward. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Vaupel DB (1983) Naltrexone fails to antagonize the sigma effects of PCP and SKF 10-047 in the dog. Eur J Pharmacol 92:269–274

    Google Scholar 

  • Wagner GC, Masters DB, Tomie A (1984) Effects of phencyclidine, haloperidol, and naloxone on fixed-interval performance in rats. Psychopharmacology 84:32–38

    Google Scholar 

  • Wauquier A, Rolls ET (1976) (eds) Brain-stimulation reward. Elsevier Biomedical Press, New York

    Google Scholar 

  • Weibel SL, Wolf HH (1979) Opiate modification of intracranial self-stimulation in the rat. Pharmacol Biochem Behav 10:71–78

    Google Scholar 

  • Wise RA (1978) Catecholamine theories of reward: a critical review. Brain Res 152:215–247

    Google Scholar 

  • Wise RA, Rompre P-P (1989) Brain dopamine and reward. Ann Rev Psychol 40:191–225

    Google Scholar 

  • Young AM (1986) Effects of acute morphine pretreatment on the rate-decreasing and antagonist activity of naloxone. Psychopharmacology 88:201–208

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, Emory University School of Medicine, 30322, Atlanta, GA, USA

    Richard P. Michael

  2. Georgia Mental Health Institute, 1256 Briarcliff Road NE, 30306, Atlanta, GA, USA

    Gerald J. Schaefer

Authors
  1. Gerald J. Schaefer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard P. Michael
    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

Schaefer, G.J., Michael, R.P. Interactions of naloxone with morphine, amphetamine and phencyclidine on fixed interval responding for intracranial self-stimulation in rats. Psychopharmacology 102, 263–268 (1990). https://doi.org/10.1007/BF02245931

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245931

Key words

Search

Navigation