Regional neuroleptic microinjections indicate a role for nucleus accumbens in lateral hypothalamic self-stimulation reward

Stellar, James R.; Corbett, Dale

doi:10.1016/0006-8993(89)91400-5

Cited by 82 publications

(40 citation statements)

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“…Evidence for dopamine's importance in ICS includes the reduced responding in rats with lesions of dopaminergic neurons (34), the blockade of ICS by NAc microinjections of a dopaminergic antagonist (16), and the impaired ICS in D1 knockout mice (12). However, measurements of dopamine release during ICS indicate that it is not a necessary condition for ICS (35).…”

Section: Discussionmentioning

confidence: 99%

“…One set of axons that occupy the MFB are the ascending neurons of the mesolimbic dopamine system that project to the NAc from their origin in the ventral tegmental area (VTA) (13,14). Because electrical stimulation with parameters that are used in ICS causes antidromic firing of dopaminergic neurons (15) and dopamine-receptor antagonists applied to the NAc inhibit ICS reinforcement (16), dopamine neurotransmission in the NAc is considered important in reward processing (17). Modern views of rewardrelated behavior ascribe an alerting or learning role to dopamine, rather than direct mediation of hedonia (2,14,18,19).…”

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confidence: 99%

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Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation

Cheer

Heien²,

Garris

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

124

128

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Intracranial self-stimulation (ICS) is a motivated behavior that results from contingent activation of the brain reward system. ICS with stimulating electrodes placed in the medial forebrain bundle (MFB) is particularly robust. However, the neurons that course through this pathway use a variety of neurotransmitters including dopamine and GABA. For this reason, the neurotransmitters that are central to this behavior, and the specific roles that they subserve, remain unclear. Here, we used extracellular electrophysiology and cyclic voltammetry at the same electrode in awake rats to simultaneously examine cell firing and dopamine release in the nucleus accumbens (NAc) during ICS and noncontingent stimulation of the MFB. ICS elicited dopamine release in the NAc and produced coincident time-locked changes (predominantly inhibitions) in the activity of a subset of NAc neurons. Similar responses were elicited with noncontingent stimulations. The changes in firing rate induced by noncontingent stimulations were reversed by the GABAA receptor antagonist bicuculline. Most time-locked unit activity was unaffected by D1 or D2-like dopamine-receptor antagonists, or by inhibition of evoked dopamine release, although, for a minority of units, the D1 dopamine-receptor antagonist SCH23390 attenuated neural activity. Thus, neurons in the NAc are preferentially inhibited by GABAA receptors after MFB stimulation, a mechanism that may also be important in ICS.cyclic voltammetry ͉ electrophysiology ͉ nucleus accumbens ͉ motivated behavior ͉ behaving rat

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation

Cheer

Heien²,

Garris

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

124

128

View full text Add to dashboard Cite

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“…In effect, there is a substantial body of evidence showing that release of DA in the nucleus accumbens plays a key role in reward. Blockade of DA receptors in this region reduces BSR (Stellar and Corbett, 1989;Nakajima and Patterson, 1997), whereas injection of amphetamine, a drug that increases local DA release, enhances reward (Colle and Wise, 1988;Ranaldi and Beninger, 1994). How can we explain the reduction effect of M100907 on the attenuation of haloperidol on reward?…”

Section: -Ht2a Receptors Blockade Reduces Reward Attenuationmentioning

confidence: 99%

Blockade of 5-HT2a Receptors Reduces Haloperidol-Induced Attenuation of Reward

Benaliouad

Kapur

Rompré

2006

Neuropsychopharmacol

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Previous studies have shown that effective antipsychotic medications attenuate reward, an effect that is generally attributed to their effectiveness at blocking the dopamine D2-like receptors. As blockade of the serotonin type 2a (5-HT2a) receptors is a common property of the newer antipsychotics, the present study compared the effect of haloperidol, clozapine, and M100907 (a selective 5-HT2a antagonist) and the combined effect of haloperidol and M100907 treatment on brain stimulation reward (BSR). Experiments were performed on male Sprague-Dawley rats trained to produce an operant response to obtain electrical stimulation in the lateral hypothalamus. Measures of reward threshold were determined in different groups of rats using the curve-shift method using fixed current intensity and variable frequency before and at different times after injection of haloperidol (0.01, 0.05, 0.1, and 0.25 mg/kg), clozapine (1, 7.5, 15, and 30 mg/kg), M100907 (0.033, 0.1, and 0.3 mg/kg), or their vehicle. The effect of M100907 (0.3 mg/kg) on the attenuation of BSR by a sub-and suprathreshold dose of haloperidol was studied in another group of rats. Clozapine produced a dose-orderly increase in reward threshold with a mean maximal increase of 50%; at high doses, clozapine induced cessation of responding in several animals at different time periods. Haloperidol induced a dose-dependent increase in reward threshold, with the mean maximal increase (75%) being observed at the highest dose; it also produced a dose-dependent reduction of maximum rates of responding. M100907 failed to alter reward at any of the doses tested and had no effect on the subthreshold dose (0.01 mg/kg) of haloperidol. But when combined with a suprathreshold dose of haloperidol, M100907 reduced the reward-attenuating effect of haloperidol. These results show that 5-HT2a receptors are unlikely to constitute a component of the reward-relevant pathway activated by lateral hypothalamic stimulation. However, blockade of 5-HT2a receptors may account for the relatively lower level of reward attenuation produced by clozapine, and predict that antipsychotic medications that have a high affinity for the 5-HT2a receptor may be less likely to induce dysphoria.

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“…ACB DA depletion, produced by 6-OH DA, abolishes or attenuates intravenous self-administration of the indirect DA agonists amphetamine and cocaine (Roberts et al, 1977;Lyness et al, 1979;Pettit et al, 1984). Microinjection of DA antagonists into the ACB disrupts operant responding maintained by electrical brain stimulation (Mora et al, 1975;Mogenson et al, 1979;Stellar et al, 1983;Stellar and Corbett, 1989) and food (Ikemoto and Panksepp, 1996). Amphetamine microinf used into the ACB facilitates brain electrical self-stimulation (Broekkamp et al, 1975;Colle and Wise, 1988) and produces place-preference conditioning (C arr andWhite, 1983, 1986).…”

Section: Abstract: Dopamine D 1 Receptor; Dopamine D 2 Receptor; Skfmentioning

confidence: 99%

Role of Dopamine D₁and D₂Receptors in the Nucleus Accumbens in Mediating Reward

et al. 1997

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The objectives of this study were to examine the involvement of D 1 and D 2 receptors within the nucleus accumbens (ACB) in mediating reinforcement. The intracranial self-administration (ICSA) of D 1 and D 2 agonists was used to determine whether activating D 1 and/or D 2 receptors within the ACB of Wistar rats is reinforcing. At concentrations of 0.25, 0.50, and 1.0 mM (25, 50, and 100 pmol/100 nl of infusion), neither the D 1 agonist R(ϩ)- 3,4,] hydrochloride nor the D 2 agonist (Ϫ)-quinpirole (Quin) hydrochloride was self-administered into the shell region of the ACB. On the other hand, equimolar mixtures of SKF and Quin (SKFϩQuin), at concentrations of 0.25, 0.50, and 1.0 mM each, were significantly self-infused into the ACB shell. The core region of the ACB did not support the ICSA of SKFϩQuin at any of these concentrations. Rats increased lever pressing when the response requirement was increased from a fixed ratio 1 (FR1) to FR3, and they responded significantly more on the infusion lever than they did on the control lever. Coadministration of either 0.50 mM R(ϩ) -7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) hydrochloride, a D 1 antagonist, or 0.50 mM S(Ϫ)-sulpiride, a D 2 antagonist, completely abolished the ICSA of the mixture of SKFϩQuin (each at 0.50 mM) into the ACB shell. The present results suggest that concurrent activation of D 1 -and D 2 -type receptors in the shell of the ACB had a cooperative effect on DA-mediated reward processes.

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Regional neuroleptic microinjections indicate a role for nucleus accumbens in lateral hypothalamic self-stimulation reward

Cited by 82 publications

References 50 publications

Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation

Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation

Blockade of 5-HT2a Receptors Reduces Haloperidol-Induced Attenuation of Reward

Role of Dopamine D₁and D₂Receptors in the Nucleus Accumbens in Mediating Reward

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Regional neuroleptic microinjections indicate a role for nucleus accumbens in lateral hypothalamic self-stimulation reward

Cited by 82 publications

References 50 publications

Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation

Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation

Blockade of 5-HT2a Receptors Reduces Haloperidol-Induced Attenuation of Reward

Role of Dopamine D1and D2Receptors in the Nucleus Accumbens in Mediating Reward

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Role of Dopamine D₁and D₂Receptors in the Nucleus Accumbens in Mediating Reward