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Effects of accumbens DALA microinjections on brain stimulation reward and behavioral activation in intact and 6-OHDA treated rats

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Abstract

The effects of bilateral nucleus accumbens microinjections ofd-ala-met-enkephalinamide (DALA) were assessed in behavioral activation and lateral hypothalamic self-stimulation (LHSS) rate-frequency curve-shift paradigms in normal and accumbens 6-OHDA (4.0 µg) treated rats. Microinjections of DALA (2.5 µg/µl) in the behavioral activation paradigm had little effect on normal activity; however, DALA administered to 6-OHDA treated rats produced a significant overall increase in locomotion. The 6-OHDA DALA-induced locomotion effect peaked at 2 weeks after 6-OHDA treatment and then returned to baseline levels by week 5 posttreatment. Using LHSS, DALA tested over a range of doses (2.5, 5, 10, 20 µg/µl) displayed a weak biphasic reward effect only at the highest dose, which was characterized by an initial suppression followed by an elevation. DALA significantly depressed initial operant motor/performance in LHSS in a dose dependent fashion. Micro-injections of the normally ineffective low dose of DALA (2.5 µg/µl) following accumbens 6-OHDA treatment produced a significant LHSS reward decrease 2 weeks posttreatment, while LHSS motor/performance was relatively unaffected. Results are discussed in terms of opiate-dopamine and limbic-motor interactions.

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References

  • Bozarth MA, Wise RA (1981) Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci 28:551–555

    Google Scholar 

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

    Google Scholar 

  • Cador M, Taylor JR, Robbins TW (1991) Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens. Psychopharmacology 104:377–385

    Google Scholar 

  • Campbell KA, Evans G, Gallistel CR (1985) A microcomputer-based method for physiologically interpretable measurement of the rewarding efficacy of brain stimulation. Physiol Behav 35:395–403

    Google Scholar 

  • Carr GD, White NM (1983) Conditioned place preference from intra-accumbens but not intra-caudate amphetamine injections. Life Sci 33:2551–2557

    Google Scholar 

  • Castaneda E, Whishaw IQ, Robinson TE (1990) Changes in striatal dopamine neurotransmission assessed with microdialysis following recovery from a bilateral 6-OHDA lesion: variation as a function of lesion size. J Neurosci 10:1847–1854

    Google Scholar 

  • Choulli K, Herman JP, Rivet JM, Simon H, LeMoal M (1987) Spontaneous and graft-induced behavioral recovery after 6-hydroxy-dopamine lesion of the nucleus accumbens in the rat. Brain Res 407:376–380

    Google Scholar 

  • Chu B, Kelley AE (1992) Potentiation of reward-related responding by psychostimulant infusion into nucleus accumbens: role of dopamine receptor subtypes. Psychobiology 20:153–162

    Google Scholar 

  • Cunningham ST, Kelley AE (1992) Opiate infusion into nucleus accumbens: contrasting effects on motor activity and responding for conditioned reward. Brain Res 588:104–114

    Google Scholar 

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

    Google Scholar 

  • Dauge V, Rossignol P, Roques BP (1989) Blockade of dopamine receptors reverses the behavioral effects of endogenous enkephalins in the Nucleus caudatus but not in the nucleus accumbens: differential involvement of delta and mu opioid receptors. Psychopharmacology 99:168–175

    Google Scholar 

  • Delfs JM, Kelley AE (1990) Microinjection of cocaine into the nucleus accumbens elicits locomotor activation in the rat. J Neurosci 10:303–310

    Google Scholar 

  • Esposito E, Cervo L, Petrillo P, Sbacchi M, Ravani A, Samanin R (1987) Dopamine denervation of the nucleus accumbens induces a selective increase in the number of delta opioid binding sites. Brain Res 436:25–29

    Google Scholar 

  • Ettenberg A, Duvauchelle CL (1988) Haloperidol blocks the conditioned place preference induced by rewarding brain stimulation. Behav Neurosci 102:687–691

    Google Scholar 

  • Evans KR, Eikelboom R (1987) Feeding induced by ventricular bromocriptine and amphetamine: a possible excitatory role for dopamine in eating behavior. Behav Neurosci 101:591–593

    Google Scholar 

  • Goeders NE, Lane JD, Smith JE (1984) Self-administration of methionone enkephalin into the nucleus accumbens. Pharmacol Biochem Behav 20:451–455

    Google Scholar 

  • Heyman GM, Kinzie DL, Seiden LS (1986) Chlorpromazine and pimozide alter reinforcement efficancy and motor performance. Psychopharmacology 88:346–353

    Google Scholar 

  • Hoebel BG, Monaco AP, Hernandez L, Aulisi EF, Stanley BG, Lenard L (1983) Self-injection of amphetamine directly into the brain. Psychopharmacology 81:158–163

    Google Scholar 

  • Jenck F, Gratton A, Wise RA (1987) Opioid receptor subtypes associated with ventral tegmental facilitation of lateral hypothalamic brain stimulation reward. Brain Res 423:34–38

    Google Scholar 

  • Koob G (1988) The functional output of the mesolimbic dopamine system. In: Kalivas P, Nemeroff C (ed) Mesocorticolimbic dopamine system. Ann NY Acad Sci, pp 216–227

  • Leith NJ (1982) Effects of apomorphine on self-stimulation responding: does the drug mimic current? Brain Res 277:129–136

    Google Scholar 

  • Lenard L, Hernandez L, Hoebel BG (1980) Self-injection of amphetamine directly into the nucleus accumbens. Proc Int Un Physiol Sci 14:2217

    Google Scholar 

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

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, Orlando, Florida

    Google Scholar 

  • Phillips AG, Fibiger HC (1978) The multivariate nature of motivated behavior elicited by electrical stimulation of the lateral hypothalamus. Curr Stud Hypothal Func 2:195–205

    Google Scholar 

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

    Google Scholar 

  • Robinson TE, Whishaw IQ (1988) Normalization of extracellular dopamine in striatum following recovery from a partial 6-OHDA lesion of the substantia nigra: a microdialysis study in freely moving rats. Brain Res 450:209–224

    Google Scholar 

  • Stellar JR, Corbett D (1989) Regional neuroleptic microinjections indicate a role for nucleus accumbens in lateral hypothalamic self-stimulation reward. Brain Res 477:126–143

    Google Scholar 

  • Stellar JR, Rice M (1989) Pharmacological basis of intracranial self-stimulation reward. In: Lieberman JM, Cooper SJ (eds) Neuropharmacological basis of reward. Oxford University Press, New York, pp 14–65

    Google Scholar 

  • Stinus L, Winnock M, Kelley AE (1985) Chronic neuroleptic treatment and mesolimbic dopamine denervation induce behavioral supersensitivity to opiates. Psychopharmacology 85:323–328

    Google Scholar 

  • Stinus L, Nadaud D. Deminiere J, Jauregui J, Hand TT, LeMoal M (1989) Chronic flupentixol treatment potentiates the reinforcing properties of systemic heroin administration. Biol Psychiatry 26:363–371

    Google Scholar 

  • Stricker EM, Zigmond MJ (1976) Brain catecholamines and the lateral hypothalamic syndrome. In: Novin D, Wyrwicka W, Bray GA (eds) Hunger. Basic mechanisms and clinical implications. Raven, New York, pp 19–32

    Google Scholar 

  • Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections ofd-amphetamine into the nucleus accumbens. Psychopharmacology 84:405–412

    Google Scholar 

  • Taylor JR, Robbins TW (1986) 6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbensd-amphetamine. Psychopharmacology 90:390–397

    Google Scholar 

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

    Google Scholar 

  • West TEG, Wise RA (1989) Nucleus accumbens injections of mu and delta but not kappa opioids facilitate hypothalamic brain stimulation reward. Soc Neurosci Abstr 20. 8:34

    Google Scholar 

  • White NM, Packard MG, Hiroi N (1991) Place conditioning with dopamine D1 and D2 agonists injected peripherally or into the nucleus accumbens. Psychopharmacology 103:271–276

    Google Scholar 

  • Wise RA (1988) Psychomotor stimulant properties of addictive drugs. Ann NY Acad Sci 537:228–234

    Google Scholar 

Download references

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Authors and Affiliations

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

    Patricia I. Johnson & J. R. Stellar

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  1. Patricia I. Johnson
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  2. J. R. Stellar
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Johnson, P.I., Stellar, J.R. Effects of accumbens DALA microinjections on brain stimulation reward and behavioral activation in intact and 6-OHDA treated rats. Psychopharmacology 114, 665–671 (1994). https://doi.org/10.1007/BF02244999

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  • DOI: https://doi.org/10.1007/BF02244999

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