Skip to main content
Log in

Naloxone blockade of amphetamine place preference conditioning

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

Abstract

Amphetamine and naloxone were examined in place conditioning, in order to study possible interactions between endogenous opioids and catecholamines in reinforcement. After initial preferences were determined, animals were conditioned with amphetamine alone (1.0 mg/kg SC), naloxone alone (0.02, 0.2 or 2.0 mg/kg SC) or combinations of amphetamine plus naloxone. A reliable, long-lasting preference for the compartment associated with amphetamine was observed, reflecting the reinforcing properties of this drug. No preference or aversion was observed in animals that received saline in both compartments. Naloxone (0.02, 0.2 and 2.0 mg/kg) produced a dose-dependent place aversion; while the lowest dose had effects similar to saline, the higher doses produced significant place aversions. Naloxone, at all three doses examined, prevented the ability of amphetamine to produce a place preference. Thus, the lowest dose of naloxone, having no effects alone in place conditioning was still able to block the reinforcing effects of amphetamine. These results suggest that the reinforcing effects of amphetamine are dependent on activation of opiate receptors, and provide further evidence that interactions between endogenous opioids and catecholamines may be important in reinforcement.

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

Access this article

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

  • Almaric M, Cline EJ, Martinez JL, Bloom FE, Koob GF (1987) Rewarding properties of beta-endorphin as measured by conditioned place preference. Psychopharmacology 91:14–19

    Google Scholar 

  • Andrews JS, Holtzman SG (1987) Effects of naloxone and diprenorphine on amphetamine-stimulated behavior in guinea pigs and rats. Neuropharmacology 26:1115–1120

    Google Scholar 

  • Andrews JS, Holtzman SG (1988) Effects ofd-amphetamine, morphine, naloxone, and drug combinations on visual discrimination in rats. Psychopharmacology 94:172–177

    Google Scholar 

  • Applegate CD, Kuczenski R, Leith NJ (1982) Naloxone-amphetamine interactions: biochemical effects in dopamine terminal regions. Soc Neurosci Abstr 8:121

    Google Scholar 

  • Aulisi EF, Hoebel BG (1983) Rewarding effects of amphetamine and cocaine in the nucleus accumbens and blockade by flupenthixol. Soc Neurosci Abstr 9:121

    Google Scholar 

  • Bain GT, Kornetsky C (1986) Naloxone attenuation of the effect of cocaine on rewarding brain stimulation. Life Sci 40:1119–1125

    Google Scholar 

  • Bechara A, van der Kooy D (1985) Opposite motivational effects of endogenous opioids in brain and periphery. Nature 314:533–534

    Google Scholar 

  • Bechara A, Zito KA, van der Kooy D (1987) Kappa receptors mediate the peripheral aversive effects of opiates. Pharmacol Biochem Behav 28:227–233

    Google Scholar 

  • Bechara A, van der Kooy D (1989) The tegmental pedunculopontine nucleus: a brain-stem output of the limbic system critical for the conditioned place preferences produced by morphine and amphetamine. J Neurosci 9:3400–3409

    Google Scholar 

  • Belluzzi JD, Stein L (1977) Enkephalin may mediate euphoria and drive-reduction reward. Nature 266:556–558

    Google Scholar 

  • Bozarth MA (1983) Opiate reward mechanisms mapped by intracranial self-administration. In: Smith JE, Lane JD (eds) The Neurobiology of opiate reward processes. Elsevier, New York, pp 331–360

    Google Scholar 

  • Bozarth MA (1987) Conditioned place preference: a parametric analysis using systemic heroin injections. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 241–274

    Google Scholar 

  • Bozarth MA, Wise RA (1981) Heroin reward is dependent on a dopaminergic substrate. Life Sci 29:1881–1886

    Google Scholar 

  • Broekkamp CLE, Phillips AG, Cools AR (1979) Facilitation of self-stimulation behavior following intracerebral microinjections of opioids into the ventral tegmental area. Pharmacol Biochem Behav 11:289–295

    Google Scholar 

  • Carboni E, Acquas E, Leone P, Di Chiara G (1989) 5HT3 receptor antagonists block morphine- and nicotine- but not amphetamine-induced reward. Psychopharmacology 97:175–178

    Google Scholar 

  • Carr GD, Phillips AG, Fibiger HC (1988) Independence of amphetamine reward from locomotor stimulation demonstrated by conditioned place preference. Psychopharmacology 94:221–226

    Google Scholar 

  • Carr GD, Fibiger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. In: Liebman JM, Cooper SJ (eds) The Neuropharmacological basis of reward. Oxford, New York, pp 264–319

    Google Scholar 

  • Carroll ME, Lac ST, Walker MJ, Kragh R, Newman T (1986) Effects of naltrexone on intravenous cocaine self-administration in rats during food satiation and deprivation. J Pharmacol Exp Ther 238:1–7

    Google Scholar 

  • Costello NL, Carlson JN, Glick SD, Bryda M (1989) Dose-dependent and baseline-dependent conditioning withd-amphetamine in the place conditioning paradigm. Psychopharmacology 99:244–247

    Google Scholar 

  • Davis WM, Smith SG (1973) Blocking of morphine based reinforcement by alpha-methyltyrosine. Life Sci 12:185–181

    Google Scholar 

  • DeRossett SE, Holtzman SG (1982) Effects of naloxone and diprenorphine on spontaneous activity in rats and mice. Pharmacol Biochem Behav 17:347–351

    Google Scholar 

  • De Vry J, Donselaar I, Van Ree JM (1989) Food deprivation and acquisition of intravenous cocaine self-administration in rats: effect of naltrexone and haloperidol. J Pharmacol Exp Ther 251:735–740

    Google Scholar 

  • Dettmar PW, Cowan A, Walter DS (1978) Naloxone antagonizes behavioral effects ofd-amphetamine in mice and rats. Neuropharmacology 17:1041–1044

    Google Scholar 

  • DiScala G, Martin-Iverson MT, Phillips AG, Fibiger HC (1985) The effects of progabide (SL 76002) on locomotor activity and conditioned place preference induced byd-amphetamine. Eur J Pharmacol 107:271–274

    Google Scholar 

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

    Google Scholar 

  • Esposito RU, Perry W, Kornetsky C (1981) Chlorpromazine and brain-stimulation reward: potentiation of effects by naloxone. Pharmacol Biochem Behav 15:903–905

    Google Scholar 

  • Ettenberg A, Pettit HO, Bloom FE, Koob GF (1982) Heroin and cocaine intravenous self-administration in rats mediation by separate neural systems. Psychopharmacology 78:204–209

    Google Scholar 

  • File SE (1986) Aversive and appetitive properties of anxiogenic and anxiolytic agents. Behav Brain Res 21:189–194

    Google Scholar 

  • Franklin KBG, Robertson A (1982) Effects and interactions of naloxone and amphetamine on self-stimulation of the prefrontal cortex and dorsal tegmentum. Pharmacol Biochem Behav 16:433–436

    Google Scholar 

  • Fudala PJ, Teoh KW, Iwamoto ET (1985) Pharmacologic characterization of nicotine-induced conditioned place preference. Pharmacol Biochem Behav 22:237–241

    Google Scholar 

  • Fulginiti S, Cancela LM (1983) Effects of naloxone and amphetamine on acquisition and memory consolidation of active avoidance responses in rats. Psychopharmacology 79:45–48

    Google Scholar 

  • Gilbert D, Cooper SJ (1983) β-phenylethylamine-,d-amphetamine-andl-amphetamine-induced place preference conditioning in rats. Eur J Pharmacol 95:311–314

    Google Scholar 

  • Glimcher PW, Giovino AA, Margolin DH, Hoebel BG (1984a) Endogenous opioid reward induced by an enkephalinase inhibitor, thiorphan, injected into the ventral midbrain. Behav Neurosci 98:262–268

    Google Scholar 

  • Glimcher PW, Margolin DH, Giovino AA, Hoebel BG (1984b) Neurotensin: a new ‘reward peptide’. Brain Res 291:119–124

    Google Scholar 

  • Haber, S, Hatsukami T, Berger PA, Barchas JD, Akil H (1978) Naloxone blocks amphetamine-induced rearing: potential interaction between catecholamines and endorphins. Prog Neuropsychopharmacol Biol Psychiatry 2:425–430

    Google Scholar 

  • Hand TH, Stinus L, Le Moal M (1989) Differential mechanisms in the acquisition and expression of heroin-induced place preference. Psychopharmacology 98:61–67

    Google Scholar 

  • Hitzemann R, Curell J, Hom D, Loh H (1982) Effects of naloxone ond-amphetamine- and apomorphine-induced behavior. Neuropharmacology 21:1005–1011

    Google Scholar 

  • Hoffman DC (1989) The use of place conditioning in studying the neuropharmacology of drug reinforcement. Brain Res Bull 23:373–387

    Google Scholar 

  • Holtzman Sg (1974) Behavioral effects of separate and combined administration of naloxone andd-amphetamine. J Pharmacol Exp Ther 180:51–60

    Google Scholar 

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

    Google Scholar 

  • Houdi AA, Bardo MT, Van Loon GR (1989) Opioid mediation of cocaine-induced hyperactivity and reinforcement. Brain Res 497:195–198

    Google Scholar 

  • Hubner CB, Bain GT, Kornetsky C (1987) The combined effect of morphine and d-amphetamine on the threshold for brain stimulation reward. Pharmacol Biochem Behav 28:311–315

    Google Scholar 

  • Katz RJ, Gormenzano G (1979) A rapid and inexpensive technique for assessing the reinforcing effects of opiate drugs. Pharmacol Biochem Behav 11:231–234

    Google Scholar 

  • Kosten TR, Kleber HD, Morgan C (1989) Role of opioid antagonists in treating intravenous cocaine abuse. Life Sci 44:887–892

    Google Scholar 

  • Leith NJ (1982) Effects of clonidine and naloxone on self-stimulation responding before and after chronic amphetamine treatment. Soc Neurosci Abstr 8:103

    Google Scholar 

  • Lyness W, Friedle N, Moore K (1979) Destruction of dopaminergic nerve terminals in nucleus accumbens: effects ond-amphetamine self-administration. Pharmacol Biochem Behav 11:553–556

    Google Scholar 

  • Mackey WB, van der Kooy D (1985) Neuroleptics block the positive reinforcing effects of amphetamine but not of morphine as measured by place conditioning. Pharmacol Biochem Behav 22:101–105

    Google Scholar 

  • Maroli A, Tsang W-K, Stutz R (1978) Morphine and self-stimulation: evidence for action on a common neural substrate. Pharmacol Biochem Behav 8:119–123

    Google Scholar 

  • Martin-Iverson MT, Ortmann R, Fibiger HC (1985) Place preference conditioning with methylphenidate and nomifensine. Brain Res 332:59–67

    Google Scholar 

  • Mithani S, Martin-Iverson MT, Phillips AG, Fibiger HC (1986) The effects of haloperidol on amphetamine- and methylphenidate-induced conditioned place preferences and locomotor activity. Psychopharmacology 90:247–252

    Google Scholar 

  • Monaco A, Hernandez L, Hoebel B (1981) Nucleus accumbens: site of amphetamine self-injection: comparison with the lateral ventrical. In: Chronister RB, DeFrance JF (ed) The neurobiology of the nucleus accumbens. Haer Institute, Brunswick, Maine, pp 338–342

    Google Scholar 

  • Mucha RF, Herz A (1985) Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology 86:274–280

    Google Scholar 

  • Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Psychopharmacology 82:241–247

    Google Scholar 

  • Mucha RF, van der Kooy D, O'Shaughnessy M, Bucenieks P (1982) Drug reinforcement studied by use of place conditioning in rat. Brain Res 243:91–105

    Google Scholar 

  • Mucha RF, Millan MJ, Herz A (1985) Aversive properties of naloxone in non-dependent (naive) rats may involve blockade of central β-endorphin. Psychopharmacology 86:281–285

    Google Scholar 

  • Neisewander JL, Pierce RC, Bardo MT (1990) Naloxone enhances the expression of morphine-induced conditioned place preference. Psychopharmacology 100:201–205

    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 

  • Phillips AG, LePiane FG (1980) Reinforcing effects of morphine microinjection into ventral tegmental area. Pharmacol Biochem Behav 12:965–968

    Google Scholar 

  • Phillips AG, LePiane FG (1982) Reward produced by microinjection of d-ala-met-enkephalinamide into the ventral tegmental area. Behav Brain Res 5:225–229

    Google Scholar 

  • Phillips AG, Spyraki C, Fibiger HC (1982) Conditioned place preference with amphetamine and opiates as reward stimuli: attenuation by haloperidol. In: Hoebel BG, Novin D (eds) The neural basis of feeding and reward. Haer Institute, Brunswick, Maine, pp 455–464

    Google Scholar 

  • Pollard H, Llorens C, Bonnet JJ, Constentin J, Schwartz JC (1977) Opiate receptors on mesolimbic dopaminergic neurons. Neurosci Lett 7:295–299

    Google Scholar 

  • Reicher MA, Holman EW (1977) Location preference and flavor aversion reinforced by amphetamine in rats. Anim Learn Behav 5:343–346

    Google Scholar 

  • Rossi NA, Reid L (1976) Affective states associated with morphine injections. Physiol Psychol 4:269–274

    Google Scholar 

  • Sherman JE, Roberts T, Roskam SE, Holman EW (1980) Temporal properties of the rewarding and aversive effects of amphetamine in rats. Pharmacol Biochem Behav 13:597–599

    Google Scholar 

  • Shippenberg TS, Herz A (1987) Place preference conditioning reveals the involvement of D1-dopamine receptors in the motivational properties of μ and κ-opioid agonists. Brain Res 436:169–172

    Google Scholar 

  • Shippenberg TS, Emmett-Oglesby M, Ayesta J, Herz A (1988) Tolerance and selective cross-tolerance to the motivational effects of opioids. Psychopharmacology 96:110–115

    Google Scholar 

  • Shippenberg TS, Emmett-Oglesby MW, Herz A (1989) Morphine-induced place conditioning is not confounded by drug-induced alterations in locomotor activity. Pharmacol Biochem Behav 32:129–132

    Google Scholar 

  • Spyraki C, Fibiger HC, Phillips AG (1982a) Cocaine-induced place preference conditioning: lack of effects of neuroleptics and 6-hydroxydopamine lesions. Brain Res 253:195–203

    Google Scholar 

  • Spyraki C, Fibiger HC, Phillips AG (1982b) Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res 253:185–193

    Google Scholar 

  • Spyraki C, Fibiger HC, Phillips AG (1983) Attenuation of heroin reward by disruption of the mesolimbic dopamine system. Psychopharmacology 79:278–283

    Google Scholar 

  • Spyraki C, Kazandjian A, Varanos D (1985) Diazepam-induced place preference conditioning: appetitive and antiaversive properties. Psychopharmacology 87:225–232

    Google Scholar 

  • Spyraki C, Nomikos GG, Varonos DD (1987) Intravenous cocaine-induced place preference: attenuation by haloperidol. Behav Brain Res 26:57–62

    Google Scholar 

  • Spyraki C, Nomikos GG, Galanopoulou P, Daïfotis Z (1988) Drug-induced place preference in rats with 5,7-dihydroxytryptamine lesions of the nucleus accumbens. Behav Brain Res 29:127–134

    Google Scholar 

  • Stapleton MJ, Lind MD, Merriman VJ, Bozarth MJ, Reid LF (1979) Affective consequences and subsequent effects on morphine self-administration ofd-ala-methionine enkephalin. Physiol Psychol 7:146–152

    Google Scholar 

  • Stein L (1978) Reward transmitters: catecholamines and opioid peptides. In: Lipton MA, DiMascio A, Killam KF (ed) Psychopharmacology: a generation of progress. Raven Press, New York, pp 569–581

    Google Scholar 

  • Swerdlow NR, Koob GF (1984) Restrained rats learn amphetamine-conditioned locmotion, but not place preference. Psychopharmacology 84:163–166

    Google Scholar 

  • Swerdlow NR, Vaccarino FJ, Koob GF (1985) Effects of nalox-one on heroin-, amphetamine- and caffeine-stimulated locomotor activity in the rat. Pharmacol Biochem Behav 23:499–501

    Google Scholar 

  • Trujillo KA, Belluzzi JD, Stein L (1983) Endorphin-catecholamine interactions in nucleus accumbens self-stimulation. Soc Neurosci Abstr 9:277

    Google Scholar 

  • Trujillo KA, Belluzzi JD, Tabrizi PR, Stein L (1985) Naloxone blockade of amphetamine reward in place preference conditioning. Soc Neurosci Abstr 11:1173

    Google Scholar 

  • Trujillo KA, Belluzzi JD, Stein L (1989a) Effects of opiate antagonists and their quaternary analogues on nucleus accumbens self-stimulation. Behav Brain Res 33:181–188

    Google Scholar 

  • Trujillo KA, Belluzzi JD, Stein L (1989b) Naloxone suppression of self-stimulation is independent of response difficulty. Pharmacol Biochem Behav 33:147–155

    Google Scholar 

  • van der Kooy D (1987) Place conditioning: a simple and effective method for assessing the motivational properties of drugs. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 229–240

    Google Scholar 

  • van der Kooy D, Mucha RF, O'Shaughnessy M, Bucenieks P (1982) Reinforcing effects of morphine revealed by conditioned place preference. Brain Res 243:107–117

    Google Scholar 

  • Vezina P, Stewart J (1987) Morphine conditioned place preference and locomotion: the effect of confinement during training. Psychopharmacology 93:257–260

    Google Scholar 

  • Watson SJ, Trujillo KA, Herman JP, Akil H (1989) Neuroanatomical and neurochemical substrates of drug seeking behavior: overview and future directions. In: Goldstein A (ed) Molecular and cellular aspects of the drug addictions. Springer, Berlin Heidelberg New York, pp 29–91

    Google Scholar 

  • Winslow JT, Miczek KA (1988) Naltrexone blocks amphetamine-induced hyperactivity, but not disruption of social and agonistic behavior in mice and squirrel monkeys. Psychopharmacology 96:493–499

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

A preliminary report of this research was presented at the 11th Annual Society for Neuroscience Meeting in Dallas, Texas (Trujillo et al. 1985)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trujillo, K.A., Belluzzi, J.D. & Stein, L. Naloxone blockade of amphetamine place preference conditioning. Psychopharmacology 104, 265–274 (1991). https://doi.org/10.1007/BF02244190

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244190

Key words

Navigation