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Injection of 5-HT into the nucleus accumbens reduces the effects ofd-amphetamine on responding for conditioned reward

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Abstract

Injection ofd-amphetamine into the nucleus accumbens potentiates responding for stimuli paired with a primary reward. A previous study showed that this potentiating effect ofd-amphetamine on responding for conditioned reward (CR) was attenuated by peripherally injectedd-fenfluramine, a 5-hydroxytryptamine (5-HT) releaser and re-uptake inhibitor. The present experiments further examined the effects of manipulating 5-HT function within the nucleus accumbens on responding for CR, and on the potentiation of CR responding following intra-accumbens injection ofd-amphetamine. Water deprived rats were trained to associate a compound stimulus with water delivery during a conditioning phase. During a test phase water was not delivered, but the compound stimulus was delivered according to a random ratio 2 schedule following a response on one of two levers. Rats responded at a higher rate on the lever delivering this CR.d-Amphetamine (10 μg) injected into the nucleus accumbens enhanced responding on the CR lever. Co-injections of 5-HT (5 and 10 μg) into the nucleus accumbens abolished the response-potentiating effect ofd-amphetamine but were without effect on the base-line level of responding for CR. This reduction by 5-HT of the response potentiating effect ofd-amphetamine was prevented by prior treatment with the 5-HT receptor antagonist metergoline (1 mg/kg). Responding for water was not altered by 5-HT and so the effects of 5-HT on responding for CR cannot be due to a change in the motivation to seek the primary reward. Thus, elevating 5-HT activity within the nucleus accumbens antagonises the effects ofd-amphetamine on responding for CR within the nucleus accumbens. These results suggest that 5-HT within the nucleus accumbens may play an important role in mediating incentive motivation by modulating dopaminergic neurotransmission.

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References

  • Beninger RJ (1983) The role of dopamine in locomotor activity and learning. Brain Res Rev 6:173–196

    Google Scholar 

  • Benloucif S, Galloway MP (1991). Facilitation of dopamine release in vivo by serotonin agonists: studies with microdialysis. Eur J Pharmacol 200:1–8

    Google Scholar 

  • Benloucif S, Keegan MJ, Galloway MP (1993) Serotonin-facilitated dopamine release in vivo: pharmacological characterization. J Pharmacol Exp Ther 265:373–377

    Google Scholar 

  • Bonhomme, N, De Deurwaerdere P, Le Moal M, Spampinato U (1995) Evidence for 5-HT4 receptor subtype involvement in the enhancement of striatal dopamine release induced by serotonin: a microdialysis study in the halothane-anesthetized rat. Neuropharmacology 34:269–279

    Google Scholar 

  • Burns LH, Everitt BJ, Kelley AE, Robbins TW (1994) Glutamate-dopamine interactions in the ventral striatum: role in locomotor activity and responding with conditioned reinforcement. Psychopharmacology 115:516–528

    Google Scholar 

  • Cador M, Robbins TW, Everitt BJ (1989) Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum. Neuroscience 30:77–86

    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 

  • Carter CJ, Pycock CJ (1978) Differential effects of central serotonin manipulation on hyperactive and stereotyped behaviour. Life Sci 23:953–960

    Google Scholar 

  • Costall B, Hui SCG, Naylor RJ (1979) The importance of serotonergic mechanisms for the induction of hyperactivity by amphetamine and its antagonism by intra-accumbens (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI). Neuropharmacology, 18:605–609

    Google Scholar 

  • Davis WM, Smith SG (1987) In: Bozarth MA Methods of assessing the reinforcing properties of abused drugs. Springer, Heidelberg, pp 199–210

    Google Scholar 

  • Fallon JH, Ciofi P (1992) Distribution of monoamines within the amygdala. In: Aggleton JP (ed) The amygdala: neurobiological aspects of emotion, memory and mental dysfunction. Wiley-Liss, New York, pp 97–114

    Google Scholar 

  • Fibiger HC, Phillips AG (1986) Reward, motivation, cognition: psychobiology of mesotelencephalic dopamine systems. In: Mountcastle VB, Bloom FE, Geiger SR (eds) Handbook of physiology: the nervous system (vol. 4). American Physiological Society, Bethesda, Maryland, pp 647–675

    Google Scholar 

  • Fletcher PJ (1995) Effects ofd-fenfluramine and metergoline on responding for conditioned reward and the response potentiating effect of nucleus accumbensd-amphetamine. Psychopharmacology 118:155–163

    Google Scholar 

  • Fletcher PJ, Ming ZH, Higgins GA (1993) Conditioned place preference induced by microinjection of 8-OH-DPAT into the dorsal or median raphe nuclei. Psychopharmacology 113:31–36

    Google Scholar 

  • Fletcher PJ, Tampakeras M, Yeomans JS (1995) Median raphe injections of 8-OH-DPAT lower frequency thresholds for lateral hypothalamic self-stimulation. Pharmacol Biochem Behav 52:65–71

    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 

  • Hokfelt T, Rehfeld JF, Skirboll L, Ivemark B, Goldstein M, Markey K (1980) Evidence for coexistence of dopamine and CCK in mesolimbic neurons. Nature 285:476–478

    Google Scholar 

  • Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PPA (1994) VII. International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46:157–203

    Google Scholar 

  • Jackson EA, Kelly PH, Schultz L (1985). Effects of serotonergic activity in nucleus accumbens septi on drug-induced circling. Neuropharmacology 24:721–727

    Google Scholar 

  • Jacocks III HM, Cox BM (1992) Serotonin-stimulated release of [3H]dopamine via reversal of the dopamine transporter in rat striatum and nucleus accumbens: a comparison with release elicited by potassium,N-methyl-D-aspartic acid, glutamic acid andd-amphetamine. J Pharmacol Exp Ther 262:356–364

    Google Scholar 

  • Jones DL, Mogenson GJ, Wu M (1981) Injections of dopaminergic, cholinergic, serotonergic and GABAergic drugs into the nucleus accumbens: effects on locomotor activity in the rat. Neuropharmacology 20:29–37

    Google Scholar 

  • Kelley AE, Delfs JM (1991) Dopamine and conditioned reinforcement I. Differential effects of amphetamine microinjections into striatal subregions. Psychopharmacology 103:187–196

    Google Scholar 

  • Loh EA, Roberts DCS (1990) Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin. Psychopharmacology 101:262–266

    Google Scholar 

  • Lyness WH, Moore KE (1981) Destruction of 5-hydroxytryptaminergic neurons and the dynamics of dopamine in nucleus accumbens septi and other forebrain regions of the rat. Neuropharmacology 20:327–334

    Google Scholar 

  • Lyness WH, Friedle NM, Moore KE (1980) Increased self-administration ofd-amphetamine after destruction of 5-hydroxytryptaminergic neurons. Pharmacol Biochem Behav 12:937–941

    Google Scholar 

  • Papp M, Willner P (1991) 8-OH-DPAT -induced place preference and place aversion: effects of PCPA and dopamine antagonists. Psychopharmacology 103:99–102

    Google Scholar 

  • Parsons LH, Justice JB Jr (1993) Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis. Brain Res 606:195–199

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, Sydney

    Google Scholar 

  • Phillips GD, Le Noury J. Wolterink G, Donselaar-Wolterink I, Robbins TW, Everitt BJ (1993) Cholecsytokinin-dopamine interactions within the nucleus accumbens in the control over behavior by conditioned reinforcement. Behav Brain Res 55:223–231

    Google Scholar 

  • Plaznik A, Danysz W, Kostowski W (1985) Some behavioural effects of microinjections of noradrenaline and serotonin into the amygdaloid body of the rat brain. Physiol Behav 34:481–487

    Google Scholar 

  • Poschel BPH, Ninteman FW (1971) Intracranial reward and the forebrain's serotonergic mechanism: studies employingpara-chlorophenylalanine andpara-chloroamphetamine. Pharmacol Biochem Behav 7:39–46

    Google Scholar 

  • Pucilowski O, Plaznik A, Kostowski W (1985) Aggressive behavior inhibition by serotonin and quipazine injected into the amygdala in the rat. Behav Neural Biol 43:58–68

    Google Scholar 

  • Redgrave P (1978) Modulation of intracranial self-stimulation behaviour by local perfusions of dopamine, noradrenaline and serotonin within the caudate nucleus and nucleus accumbens. Brain Res 155:277–295

    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 responding with reward-related stimuli produced by intra-accumbensd-amphetamine. Psychopharmacology 90:390–397

    Google Scholar 

  • Schiavi GB, Brunet S, Rizzi CA, Ladinsky H (1994) Identification of serotonin 5-HT4 recognition sites in the porcine caudate nucleus by radioligand binding. Neuropharmacology 33: 543–549

    Google Scholar 

  • Waeber C, Serben M, Nieoullon A, Bockaert J, Dumuis A (1994). Regional distribution and ontogeny of 5-HT4 binding sites in rodent brain. Neuropharmacology 33:527–541

    Google Scholar 

  • Wang RY, Aghajanian GK (1977) Inhibition of neurons in the amygdala by dorsal raphe stimulation: mediation through a direct serotonergic pathway. Brain Res 120:85–102

    Google Scholar 

  • Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225

    Google Scholar 

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Fletcher, P.J. Injection of 5-HT into the nucleus accumbens reduces the effects ofd-amphetamine on responding for conditioned reward. Psychopharmacology 126, 62–69 (1996). https://doi.org/10.1007/BF02246412

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  • DOI: https://doi.org/10.1007/BF02246412

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