Skip to main content
Log in

Dopamine and endogenous opioid regulation of picrotoxin-induced locomotion in the ventral pallidum after dopamine depletion in the nucleus accumbens

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

Abstract

Microinjection of picrotoxin or the μ-opioid agonist, Tyr-D-Ala-Gly-NmePhe-Gly-OH (DAMGO), into the ventral pallidum (VP) produces an increase in locomotor activity that is antagonized by dopamine receptor blockade. To investigate the regulation of VP-induced locomotion by the dopaminergic innervation of the nucleus accumbens (NA) and the role of opioid receptors in this regulation, dopamine innervation of the NA was bilaterally lesioned with 6-hydroxydopamine (6-OHDA). The lesions resulted in an 89–97% depletion of tissue dopamine levels in the nucleus accumbens compared with sham-lesioned rats. Dopamine depletion in the NA failed to significantly antagonize picrotoxin or DAMGO injected into the VP. However, the dopamine receptor antagonist, haloperidol (0.1 mg/kg, IP), blocked the picrotoxin-initiated increase in horizontal photocell counts in both sham- and 6-OHDA-lesioned rats. The opioid receptor antagonist, naloxone (1.0 mg/kg, SC), also blocked the picrotoxin-induced locomotion in 6-OHDA-lesioned rats but did not block locomotion in the sham-lesioned rats. At a higher dose (3.0 mg/kg, SC), naloxone blocked picrotoxin-induced locomotion in both sham- and 6-OHDA-lesioned rats. These results indicate that although dopamine depletion in the NA does not affect the permissive role of dopamine transmission on locomotion elicited from the VP, it results in an increased sensitivity to enkephalinergic transmission.

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

  • Austin MC, Kalivas PW (1988) The effect of cholinergic stimulation in the nucleus accumbens on locomotor behavior. Brain Res 441:209–214

    Article  PubMed  Google Scholar 

  • Austin MC, Kalivas PW (1989) Blockade of enkephalinergic and GABAergic mediated locomotion in the nucleus accumbens by muscimol in the ventral pallidum. Jpn J Pharmacol 50:487–490

    PubMed  Google Scholar 

  • Austin MC, Kalivas PW (1990) Enkephalinergic and GABAergic modulation of motor activity in the ventral pallidum. J Pharmacol Exp Ther 252:1370–1377

    PubMed  Google Scholar 

  • Austin MC, Kalivas PW (1991) Dopaminergic involvement in locomotion elicited from the ventral pallidum/substantia innominata. Brain Res 542:123–131

    Article  PubMed  Google Scholar 

  • Churchill L, Kalivas PW (1992) Dopamine depletion produces augmented behavioral responses to a μ-, but not δ-opioid receptor agonist in the nucleus accumbens: lack of a role for receptor upregulation. Synapse (in press)

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

    Google Scholar 

  • Gerfen CR, Herkenham M, Thibault J (1987) The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. J Neurosci 7:3915–3934

    PubMed  Google Scholar 

  • Haber SN, Groenewegen HJ, Grove EA, Nauta WJH (1985) Efferent connections of the ventral pallidum: evidence of a dual striato pallidofugal pathway. J Comp Neurol 235:322–335

    Article  PubMed  Google Scholar 

  • Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltman C (1991) Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41:89–125

    Article  PubMed  Google Scholar 

  • Lalivas PW, Bronson M (1985) Mesolimbic dopamine lesions produce an augmented behavioral response to enkephalin. Neuropharmacology 24:931–936

    Article  PubMed  Google Scholar 

  • Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522

    Article  PubMed  Google Scholar 

  • Klitenick MA, Deutch AY, Churchill L, Kalivas PW (1992) Topography and functional role of dopaminergic projections from the ventral mesencephalic tegmentum to the ventral pallidum. Neuroscience (in press)

  • Milliken GA, Johnson DE (1984) Analysis of messy data vol 1.: Designed experiments. Lifetime Learning Publications, Belmont, CA, pp 326–337

    Google Scholar 

  • Mogenson GJ, Nielsen MA (1983) Evidence that an accumbens to subpallidal GABAergic projection contributes to locomotor activity. Brain Res Bull 11:309–314

    Article  PubMed  Google Scholar 

  • Mogenson GJ, Swanson LW, Wu M (1985) Evidence that projections from substantia innominata to zona incerta and mesencephalic locomotor region contribute to locomotor activity. Brain Res 334:65–76

    Article  PubMed  Google Scholar 

  • Mogenson GJ, Ciriello J, Garland J, Wu M (1987) Ventral pallidum projections to mediodorsal nucleus of the thalamus: an anatomical and electrophysiological investigation in the rat. Brain Res 404:221–230

    Article  PubMed  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, New York, pp 1–118

    Google Scholar 

  • Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Plenum Press, New York, pp 1–122

    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

    Article  PubMed  Google Scholar 

  • Swerdlow NR, Koob GF (1987) Lesions of the dorsomedial nucleus of the thalamus, medial prefrontal cortex and pedunculopontine nucleus: effects on locomotor activity mediated by nucleus accumbens-ventral pallidal circuitry. Brain Res 412:233–243

    Article  PubMed  Google Scholar 

  • Swerdlow NR, Vaccarino FJ, Amalric M, Koob GF (1986) The neural substrates for the motor-activating properties of psycho-stimulants: a review of recent findings. Pharmacol Biochem Behav 25:233–248

    Article  PubMed  Google Scholar 

  • Thal LJ, Sharpless NS, Hirschhorn ID, Horowitz SG, Makman MH (1983) Striatal met-enkephalin concentration increases following nigrostriatal denervation. Biochem Pharmacol 32:3297–3301

    Article  PubMed  Google Scholar 

  • Vernier P, Julien J-F, Rataboul P, Fourrier O, Feuerstein C, Mallet J (1988) Similar time course changes in striatal levels of glutamic acid decarboxylase and proenkephalin mRNA following dopaminergic deafferentation in the rat. J Neurochem 51:1375–1380

    PubMed  Google Scholar 

  • Vives F, Mogenson GJ (1985) Electrophysiological evidence that the mediodorsal nucleus of the thalamus is a relay between the ventral pallidum and the medial prefrontal cortex in the rat. Brain Res 344:329–337

    Article  PubMed  Google Scholar 

  • Voorn P, Roest G, Groenewegen HJ (1987) Increase of enkephalin and decrease of substance P immunoreactivity in the dorsal and ventral striatum of the rat after midbrain 6-hydroxydopamine lesions. Brain Res 412:391–396

    Article  PubMed  Google Scholar 

  • Zahm DS, Zaborszky L, Alones VE, Heimer L (1985) Evidence for the coexistence of glutamate decarboxylase and met-enkephalin immunoreactivities in axon terminals of rat ventral pallidum. Brain Res 325:317–321

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Churchill, L., Austin, M.C. & Kalivas, P.W. Dopamine and endogenous opioid regulation of picrotoxin-induced locomotion in the ventral pallidum after dopamine depletion in the nucleus accumbens. Psychopharmacology 108, 141–146 (1992). https://doi.org/10.1007/BF02245299

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245299

Key words

Navigation