Skip to main content

Advertisement

SpringerLink
Log in

Pharmacological dissociation between the spatial learning deficits produced by morphine and diazepam

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

Abstract

This study sought to determine whether the place learning deficits produced by diazepam are a secondary result of opioid release. Rats pretreated with diazepam (3 mg/kg) or morphine (15 mg/kg) were trained in the Morris water maze. Diazepam impaired place learning-slowing acquisition and preventing the formation of a quadrant preference. Morphine also slowed acquisition, but did not prevent place learning, and impaired escape to a visible platform. Flumazenil blocked the deficits produced by diazepam, but not morphine. Naloxone (2 mg/kg) blocked the deficits produced by morphine, but not diazepam. A high dose of naloxone (10 mg/kg) slowed acquisition, and exacerbated the deficit produced by diazepam. These results demonstrate that diazepam interferes with mnemonic processes through endogenous benzodiazepine receptors, independently of opioidergic systems. Further, they suggest that morphine interferes with motivational processes through opioidergic systems, independently of endogenous benzodiazepine systems.

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

  • Arolfo MP, Brioni JD (1991) Diazepam impairs place learning in the Morris water maze. Behav Neural Biol 55:131–136

    Article  PubMed  Google Scholar 

  • Barta A, Yashpal K (1981) Regional redistribution of β-endorphin in the rat brain: The effect of stress. Prog Neuro Psychopharmacol 5:595–598

    Article  Google Scholar 

  • Billingsley ML, Kubena RK (1978) The effects of naloxone and picrotoxin on the sedative and anticonflict effects of benzodiazepines. Life Sci 22:897–906

    Article  PubMed  Google Scholar 

  • Canli TC, Cook RG, Miczek KA (1990) Opiate antagonists enhance the working memory of rats in the radial maze. Pharmacol Biochem Behav 36:521–525

    Article  PubMed  Google Scholar 

  • Chang KJ, Hazum E, Cuatrecasas P (1980) Multiple opiate receptors. TINS 3:160–162

    Google Scholar 

  • Chapman CR, Feather BW (1973) Effects of diazepam on human pain tolerance and pain sensitivity. Psychosom Med 35:330–340

    PubMed  Google Scholar 

  • Cole SO (1986) Effects of benzodiazepines on acquisition and performance: a critical assessment. Neurosci Biobehav Rev 10:265–272

    Article  PubMed  Google Scholar 

  • Cooper SJ (1983) Benzodiazepine-opiate antagonist interactions in relation to feeding and drinking behavior. Life Sci 32:1043–1051

    Article  PubMed  Google Scholar 

  • Decker MW, Introini-Collison IB, McGaugh JL (1989) Effects of naloxone on Morris water maze learning in the rat: enhanced acquisition with pretraining but not posttraining administration. Psychobiology 17:270–275

    Google Scholar 

  • Dingledine R, Iversen LL, Breuker E (1978) Naloxone as a GABA antagonist: evidence from iontophoretic, receptor binding and convulsant studies. Eur J Pharmacol 47:19–27

    Article  PubMed  Google Scholar 

  • Duka T, Wuster M, Herz A (1979) Rapid changes in enkephalin levels in rat striatum and hypothalamus induced by diazepam. Naunyn-Schmiedeberg's Arch Pharmacol 309:1–5

    Article  Google Scholar 

  • Duka T, Wuster M, Herz A (1980) Benzodiazepines modulate striatal enkephalin levels via a GABAergic mechanism. Life Sci 26:771–776

    Article  PubMed  Google Scholar 

  • Duka T, Cumin R, Haefely W, Herz A (1981) Naloxone blocks the effect of diazepam and meprobamate on conflict behavior in rats. Pharmacol Biochem Behav 15:115–117

    Article  PubMed  Google Scholar 

  • Duka T, Millan MJ, Ulsamer B, Doenicke E (1982) Naloxone attenuates the anxiolytic action of diazepam in man. Life Sci 31:1833–1836

    Article  PubMed  Google Scholar 

  • Ghoneim MM, Mewaldt SP (1990) Benzodiazepines and human memory: a review. Anestesiology 72:926–938

    Google Scholar 

  • Harsing LG, Yang HYT, Costa E (1982) Evidence for a γ-aminobutyric acid (GABA) mediation in the benzodiazepine inhibition of the release of met5-enkephalin elicited by depolarization. J Pharmacol Exp Ther 220:616–620

    PubMed  Google Scholar 

  • Houser VP, Pare WP (1973) Analgesic potency of sodium salicylate, indomethacine, and chlordiazepoxide as measured by a spatial preference technique in the rat. Psychopharmacology 32:121–131

    Article  Google Scholar 

  • Kuriyama K, Yoneda Y (1978) Morphine induced alterations of γ-aminobutyric acid and taurine contents andl-glutamate decarboxylase activity in rat spinal cord and thalamus: possible correlates with analgesic action of morphine. Brain Res 148:163–179

    Article  PubMed  Google Scholar 

  • Lal H, Kumar B, Forester MJ (1988) Enhancement of learning and memory in mice by a benzodiazepine antagonist. FASEB J 2:2707–2711

    PubMed  Google Scholar 

  • Lista A, Blier P, De Montigny C (1989) In vivo presynaptic modulation of serotonergic neurotransmission in the rat hippocampus by diazepam. Eur J Pharmacol 171:229–231

    Article  PubMed  Google Scholar 

  • Lopez F, Miller LG, Thompson ML, Schatzki A, Chesley S, Greenblatt DJ, Shader RI (1990) Chronic morphine administration augments benzodiazepine binding and GABAA receptor function. Psychopharmacology 101:545–549

    Article  PubMed  Google Scholar 

  • McNamara RK, Skelton RW (1991a) Diazepam impairs acquisition but not performance in the Morris water maze. Pharmacol Biochem Behav 38:651–658

    Article  PubMed  Google Scholar 

  • McNamara RK, Skelton RW (1991b) Pretraining morphine impairs acquisition and performance in the Morris water maze. Motivation reduction rather than amnesia. Psychobiology 19:313–322

    Google Scholar 

  • McNamara RK, Whishaw IQ (1990) Blockade of hoarding in rats by diazepam: An analysis of the anxiety and object value hypothesis of hoarding. Psychopharmacology 101:214–221

    Google Scholar 

  • Miller LG, Kastin AJ, Greenblatt DJ (1987) Tyr-MIF-1 augments benzodiazepine receptor binding in vivo. Pharmacol Biochem Behav 28:521–524

    Article  PubMed  Google Scholar 

  • Moroni F, Cheney DL, Peralta E, Costa E (1978) Opiate receptor agonists as modulators of γ-aminobutyric acid turnover in the nucleus caudate, globus pallidus and substantia nigra of the rat. J Pharmacol Exp Ther 207:870–877

    PubMed  Google Scholar 

  • Morris RGM (1981) Spatial localization does not require the presence of local cues. Learn Motiv 12:239–260

    Article  Google Scholar 

  • Morris RGM (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Method 11:47–60

    Article  Google Scholar 

  • Paterson SJ, Robson LE, Kosterlitz HW (1983) Classification of opioid receptors. Br Med Bull 39:31–36

    PubMed  Google Scholar 

  • Raffalli-Sebille MJ, Chapouthier G (1991) Similar effects of a beta-carboline and of flumazenil in negatively and positively reinforced learning tasks in mice. Life Sci 48:685–692

    Article  PubMed  Google Scholar 

  • Sansone M, Vetulani J (1988) Effect of naloxone on the locomotor stimulatory action of chlordiazepoxide in mice. Pharmacol Biochem Behav 31:371–373

    Article  PubMed  Google Scholar 

  • Sarter M, Bruno JP, Dudchenko P (1990) Activating the damaged basal forebrain cholinergic system: tonic stimulation versus signal amplification. Psychopharmacology 101:1–17

    Google Scholar 

  • Smith JE, Co C, Lane JD (1984) Limbic muscarinic cholinergic and benzodiazepine receptor changes with chronic intravenous morphine and self-administration. Pharmacol Biochem Behav 20:443–450

    Google Scholar 

  • Soubrie P, Jobert A, Thiebot MH (1980) Differential effects of naloxone against the diazepam-induced release of behavior in rats in three aversive situations. Psychopharmacology 69:101–105

    Article  PubMed  Google Scholar 

  • Stapleton JM, Lind MD, Merriman VJ, Reid LD (1979) Naloxone inhibits diazepam-induced feeding in rats. Life Sci 24:2421–2426

    Article  PubMed  Google Scholar 

  • Stryker TD, Conlin T, Reichlin S (1986) Influence of a benzodiazepine, midazolam, and gamma-aminobutyric acid (GABA) on basal somatostatin secretion from cerebral and diencephalic neurons in dispersed cell culture. Brain Res 362:339–343

    Article  PubMed  Google Scholar 

  • Tripp G, McNaughton N (1987) Naloxone fails to block the effects of chlordiazepoxide on acquisition and performance of successive discrimination. Psychopharmacology 91:119–121

    Article  PubMed  Google Scholar 

  • Tripp G, McNaughton N (1991) Naloxone and chlordiazepoxide: effects on acquisition and performance of signalled punishment. Pharmacol Biochem Behav 38:43–47

    Article  PubMed  Google Scholar 

  • Tripp G, McNaughton N, Oei TPS (1987) Naloxone blocks the effects of chlordiazepoxide on acquisition but not performance of a differential reinforcement of low rates of response (DRL). Psychopharmacology 91:112–118

    Article  PubMed  Google Scholar 

  • Wolkowitz OM, Weingartner H, Thompson K, Pickard D, Paul SM, Hommer DW (1987) Diazepam-induced amnesia: a neuropharmacological model of an “organic amnestic syndrome”. Am J Psychiatry 144:25–29

    PubMed  Google Scholar 

  • Wuster M, Duka T, Herz A (1980a) Diazepam-induced release of opioid activity in the rat brain. Neurosci Lett 16:335–337

    Article  PubMed  Google Scholar 

  • Wuster M, Duka T, Herz A (1980b) Diazepam effects on striatal met-enkephalin levels following long-term pharmacological manipulations. Neuropharmacology 19:501–505

    Article  PubMed  Google Scholar 

  • Yang X, Lou Z, Zhou J (1988) Behavioral evidence for the role of noradrenaline in putative anxiolytic and sedative effects of benzodiazepines. Psychopharmacology 95:280–286

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology, University of Victoria, P.O. BOX 3050, V8W 3P5, Victoria, B.C., Canada

    Robert K. McNamara & Ronald W. Skelton

Authors
  1. Robert K. McNamara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronald W. Skelton
    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

McNamara, R.K., Skelton, R.W. Pharmacological dissociation between the spatial learning deficits produced by morphine and diazepam. Psychopharmacology 108, 147–152 (1992). https://doi.org/10.1007/BF02245300

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245300

Key words

Search

Navigation