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Opioid and GABA modulation of accumbens-evoked ventral pallidal activity

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Summary

The principle output of the nucleus accumbens innervates the ventral pallidum and rostral substantia innominata. GABA and opioid peptides are among the neurotransmitter candidates for this projection. The goal of the present experiments was to delineate further the physiology and pharmacology of the accumbens projection to the ventral pallidum. The trans-synaptic responsiveness of ventral pallidal and rostral substantia innominata neurons to electrical stimulation of the nucleus accumbens was examined concurrently with the ability of microiontophoretically applied morphine (an opioid agonist), naloxone (an opioid antagonist) and bicuculline (a GABA antagonist) to modulate evoked responses. Accumbens stimulation altered the firing rate in 60% of the 132 neurons tested. Fifty-two percent of responding neurons exhibited simple excitations or inhibitions in response to accumbens stimulation, while 48% exhibited complex response sequences with two or more evoked components. Predominant responses consisted of a short latency (<10 ms) and short duration (10 ms) excitation (51 % of responding neurons) and an inhibition with a variable, onset latency and, duration (52% of responding neurons). Evoked responses often occurred within limited areas within the ventral pallidum suggesting that activation of descending afferents can influence discrete targets within the region. A large majority (>80%) of neurons evoked by accumbens stimulation also exhibited a current-dependent and naloxone-sensitive increase in spontaneous firing to microiontophoretically applied morphine. Morphine shortened the duration of the accumbens-evoked, short latency excitation and attenuated the magnitude of the long-latency inhibition. Evoked responses in the presence of morphine were opposite to those observed with naloxone, but similar to bicuculline. Thus, opioid receptor activation may be functionally antagonistic to GABAergic neurotransmission in the ventral pallidum. The prominence of accumbens-evoked and morphine-sensitive neurons within the ventral pallidum corroborates the density of accumbens and opioid input to this brain region, and demonstrates that opioids serve as an important influence on neuronal activity and information processing in the ventral-striatopallidal pathway.

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References

  • Abou-Khalil B, Young AB, Penney JB (1984) Evidence for the presynaptic localization of opiate binding sites on striatal efferent fibers. Brain Res 323: 21–29

    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

    Google Scholar 

  • Bartfai T, Iverfeldt K, Brodin E, Ogren S-O (1986) Functional consequences of coexistence of classical and peptide neurotransmitters. In: Hokfelt T, Fuxe K, Pernow B (eds) Progress in brain research, vol 68. Elsevier, New York, pp 321–330

    Google Scholar 

  • Bos van den R, Cools AR (1991) Motor activity and the GABA-A receptor in the ventral pallidal/substantia innominata complex. Neurosci Lett 124: 246–250

    Google Scholar 

  • Chavkin C (1988) Electrophysiology of opiates and opioid peptides. In: Pasternak GW (ed) The opiate receptors. Humana Press, Clifton NJ, pp 273–291

    Google Scholar 

  • Dewar D, Jenner P, Marsden CD (1987) Effects of opioid agonist drugs on the in vivo release of3H-GABA,3H-dopamine and3H-5HT from slices of rat globus pallidus. Biochem Pharmacol 36: 1738–1741

    Google Scholar 

  • Duka TH, Schubert P, Wuster M, Stoiber R, Herz A (1981) A selective distribution pattern of different opiate receptors in certain areas of rat brain as revealed by in vitro autoradiography. Neurosci Lett 21: 119–124

    Google Scholar 

  • Dun NJ (1985) Substance P. In: Rogawski MA, Barker JL (eds) Neurotransmitter actions in the vertebrate nervous system. Plenum Press, New York, pp 385–410

    Google Scholar 

  • Fuller TA, Russchen FT, Price JL (1987) Sources of presumptive glutamatergic/aspartergic afferents to the rat ventral striatopallidal region. J Comp Neurol 258: 317–338

    Google Scholar 

  • Gaykema RPA, Van Weeghel RV, Hersh LB, Luiten PGM (1991) Prefrontal cortical projections to the cholinergic neurons in the basal forebrain. J Comp Neurol 303: 563–583

    Google Scholar 

  • Groenewegen HJ, Berendse HW, Meredith GE, Haber SN, Voorn P, Wolters JG, Lohman AH (1991) Functional anatomy of the ventral, limbic system-innervated striatum. In: Willner P, Scheel-Kruger J (eds) The mesolimbic dopamine system: from motivation to action. Wiley, New York, pp 19–59

    Google Scholar 

  • Hakan RL, Henriksen SJ (1989) Opiate influences on nucleus accumbens neuronal electrophysiology: dopamine and non-dopamine mechanisms. J Neurosci 9: 3538–3646

    Google Scholar 

  • Heimer L, Wilson RD (1975) The subcortical projections of the allocortex: similarities in the neural association of the hippocampus, the piriform cortex, and the neocortex. In: Santini M (ed) Golgi Centennial Symposium. Raven Press, New York, pp 177–193

    Google Scholar 

  • Hoffman DC, West TEG, Wise RA (1991) Ventral pallidal microinjections of receptor-selective opioid agonists produce differential effects on circling and locomotor activity in rats. Brain Res 550: 205–212

    Google Scholar 

  • Huffman RD, Felpel LP (1981) A microiontophoretic study of morphine on single neurons in the rat globus pallidus. Neurosci Lett 22: 195–199

    Google Scholar 

  • Jiang ZG, North RA (1992) Pre- and postsynaptic inhibition by opioids in rat striatum. J Neurosci 12: 356–361

    Google Scholar 

  • Johnson SW, North RA (1992) Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12: 483–488

    Google Scholar 

  • Jones DL, Mogenson GJ (1980) Nucleus accumbens to globus pallidus GABA projection: electrophysiological and iontophoretic investigations. Brain Res 188: 93–105

    Google Scholar 

  • Lahti RA, Mickelson MM, Jodelis KS, McCall JM (1989) Comparative neuroanatomical distribution of theK andu opioid receptors in guinea pig brain sections. Eur J Pharmacol 166: 563–566

    Google Scholar 

  • Levine MS, Hull CD, Buchwald NA (1974) Pallidal and entopeduncular intracellular responses to striatal, cortical, thalamic, and sensory inputs. Exp Neurol 44: 448–460

    Google Scholar 

  • Madison DV, Nicoll RA (1988) Enkephalin hyperpolarizes interneurones in the rat hippocampus. J Physiol 398: 123–130

    Google Scholar 

  • Malliani A, Purpura DP (1967) Intracellular studies of the corpus striatum. II. Patterns of synaptic activities in lenticular and entopeduncular neurons. Brain Res 6: 341–354

    Google Scholar 

  • Maslowski RJ, Napier TC (1991) D1 and D2 dopamine agonists induce opposite changes in the firing rate of ventral pallidal neurons. Eur J Pharmacol 200: 103–112

    Google Scholar 

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

    Google Scholar 

  • Mogenson GJ, Yang CR (1991) Contribution of basal forebrain to limbic-motor integration and the mediation of motivation to action. In: Napier TC, Kalivas P, Hanin I (eds) The basal forebrain: anatomy to function. Plenum Press, New York, pp 267–290 (Adv Exp Med Biol, vol 295)

    Google Scholar 

  • Mogenson GJ, Swanson LW, Wu M (1983) Neural projections from nucleus accumbens to globus pallidus, substantia innominata and lateral preoptic-lateral hypothalamic area: an anatomical and electrophysiological investigation in the rat. J Neurosci 3: 189–202

    Google Scholar 

  • Moskowitz AS, Goodman RR (1984) Light microscopic autoradiographic localization ofmu anddelta opioid binding sites in the mouse central nervous system. J Neurosci 4: 1331–1342

    Google Scholar 

  • Napier TC (1992) Contribution of the amygdala and nucleus accumbens to ventral pallidal responses to dopamine agonists. Synapse 10: 110–119

    Google Scholar 

  • Napier TC (1992) Ventral pallidal dopamine receptors regulate circling induced by ventral pallidal opioids. Neuropharmacology 31: 1127–1136

    Google Scholar 

  • Napier TC, Chrobak JJ, Yew (1992) Systemic and microiontophoretic administration of morphine differentially effect ventral pallidum/substantia innominata neuronal activity. Synapse 12: 214–219

    Google Scholar 

  • Napier TC, Pirch JH, Strahlendorf HK (1983) Naloxone antagonizes striatally-induced suppression of globus pallidus unit activity. Neuroscience 9: 53–59

    Google Scholar 

  • Napier TC, Simson PE, Givens BS (1991) Dopamine electrophysiology of ventral pallidal/substantia innominata neurons: comparison with the dorsal globus pallidus. J Pharmacol Exp Ther 258: 249–262

    Google Scholar 

  • Napier TC, Muench MB, Maslowski RJ, Battaglia G (1992) Is dopamine a neurotransmitter in the ventral pallidum/substantia innominanta. In: Napier TC, Kalivas P, Hanin I (eds) The basal forebrain: anatomy to function. Plenum Press, New York, pp 183–196 (Adv Exp Med Biol, vol 295)

    Google Scholar 

  • North RA (1993) Opioid action in membrane ion channels. Handbook Exp Pharmacol 104: 773–793

    Google Scholar 

  • North RA, Williams JT (1985) On the potassium conductance increased by opioids in rat locus coeruleus neurones. J Physiol 364: 265–280

    Google Scholar 

  • Obata K, Yoshida M (1973) Caudate evoked inhibition and action of GABA and other substances on cat pallidal neurons. Brain Res 64: 455–459

    Google Scholar 

  • Ohye C, Le Guyader C, Feger J (1976) Responses of subthalamic and pallidal neurons to striatal stimulation: an extracellular study on awake monkeys. Brain Res 111: 241–252

    Google Scholar 

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

    Google Scholar 

  • Pilapil C, Welner S, Magnan J, Gauthier S, Quirion R (1987), Autoradiographic distribution of multiple classes of opioid receptor binding sites in human forebrain. Brain Res Bull 19: 611–615

    Google Scholar 

  • Reiner A, Anderson KD (1990) The pattern of neurotransmitter and neuropeptide co-occurrence among striatal projection neurons: conclusions based on recent findings. Brain Res Rev 15: 251–265

    Google Scholar 

  • Richardson RT, DeLong MR (1991) Electrophysiological studies of the functions of the nucleus basalis in primates. In: Napier TC, Kalivas P, Hanin I (eds) The basal forebrain: anatomy to function. Plenum Press, New York, pp 233–252 (Adv Exp Med Biol, vol 295)

    Google Scholar 

  • Shreve PE, Uretsky NJ (1988) Effect of GABAergic transmission in the subpalidal region on the hypermotility response to the administration of excitatory amino acids and picrotoxin into the nucleus accumbens. Neuropharmacology 27: 1271–1277

    Google Scholar 

  • Spencer HJ (1976) Antagonism of cortical excitation of striatal neurons by glutamic acid diethyl ester: evidence for glutamic acid as an excitatory transmitter in the rat striatum. Brain Res 102: 91–101

    Google Scholar 

  • Swerdlow NR, Koob G (1987) Lesions of the dorsomedial nucleus of the thalamus, medial prefrontal cortex and peduncolopontine nucleus: effects on locomotor activity mediated by nucleus accumbens-ventral pallidal circuitry. Brain Res 412: 233–238

    Google Scholar 

  • Swerdlow NR, Koob GF (1987) Dopamine schizophrenia, mania and depression: towards a unified hypothesis of cortico-striato-pallido-thalamic function. Behav Brain Sci 10: 197–210

    Google Scholar 

  • Walaas I, Fonnum F (1979) The distribution and origin of glutamate decarboxylase and choline acetyltransferase in ventral pallidum and other basal forebrain regions. Brain Res 177: 325–336

    Google Scholar 

  • Yang CR, Mogenson GJ (1985) An electrophysiological study of the neural projections from the hippocampus to the ventral pallidum and the subpallidal areas by way of the nucleus accumbens. Neuroscience 15: 1015–1024

    Google Scholar 

  • Yim CR, Mogenson GJ (1983) Response of ventral pallidal neurons to amygdala stimulation and its modulation by dopamine projections to nucleus accumbens. J Neurophysiol 50: 148–161

    Google Scholar 

  • Yoshida M, Rabin A, Anderson M (1971) Two types of monosynaptic inhibition of pallidal neurons produced by stimulation of the diencephalon and substantia nigra. Brain Res 30: 235–239

    Google Scholar 

  • Zaborszky L, Cullinan WE, Braun A (1991) Afferents to basal forebrain cholinergic projection neurons: an update. In: Napier TC, Kalivas P, Hanin I (eds) The basal forebrain: anatomy to function. Plenum Press, New York, pp 1–42 (Adv Exp Med Biol, vol 295)

    Google Scholar 

  • Zahm DS (1989) The ventral striatopallidal parts of the basal ganglia in the rat. II. Compartmentation of ventral pallidal efferents. Neuroscience 30: 33–50

    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

    Google Scholar 

  • Zieglgansberger W, French ED, Siggins GR, Bloom FE (1979) Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory neurons. Science 205: 415–417

    Google Scholar 

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Chrobak, J.J., Napier, T.C. Opioid and GABA modulation of accumbens-evoked ventral pallidal activity. J. Neural Transmission 93, 123–143 (1993). https://doi.org/10.1007/BF01245342

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