increased dopamine and serotonin metabolism in rat nucleus accumbens produced by intracranial self-stimulation of medial forebrain bundle as measured by in vivo microdialysis

Nakahara, Daiichiro; Ozaki, Norio; Miura, Yoshiaki; Matsui, Hideki; Nagatsu, Toshiharu

doi:10.1016/0006-8993(89)91234-1

Cited by 90 publications

(33 citation statements)

References 16 publications

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“…These findings show that M100907 has an attenuating effect on DA-mediated behaviors. As diencephalic rewarding stimulation increases DA and 5-HT neurotransmission (Blaha and Phillips, 1990;Nakahara et al, 1989Nakahara et al, , 1992 and is very sensitive to changes in ventral midbrain neurotransmission, M100907 should have attenuated BSR. This suggests then that 5-HT2a receptors do not have such a modulatory role in the reward-relevant DA pathway activated by diencephalic electrical stimulation.…”

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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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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“…At least 3 days after surgery, the rats were reanesthetized with chloral hydrate (400 mg/kg i.p.). The dummy probe was removed from the previously described guide tube and a dialysis probe (4 mm length, 0.25 mm o.d., 5,000 MW cutoff) was inserted [19,20]. Additional chloral hydrate was administered as needed to maintain light anesthesia throughout the experiment.…”

Section: Methodsmentioning

confidence: 99%

Differential Effect of Haloperidol on Dopamine Release and Metabolism in Caudate Putamen and Anteromedial Frontal Cortex Using Intracerebral Dialysis

Kurata

Shibata

1991

Pharmacology

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The differential effects of haloperidol on dopamine release and its metabolism were investigated in the anteromedial frontal cortex and the caudate putamen using the intracerebral dialysis method in anesthetized rats after single intraperitoneal injections of 0.01, 0.125 and 2 mg/kg haloperidol. The basal levels of dopamine, 3,4-dihydroxyphenyl-acetic acid and homovanillic acid, collected every 20 min from the caudate putamen, were 22, 7.7 × 103 and 5.5 × 103 pg/30 μl, respectively, and were much higher than those from the anteromedial frontal cortex, which were 1.8, 2.6 × 102 and 4.6 × 102 pg/30 μl, respectively. There was a clear difference in the time-response curve of dopamine release between the two brain regions after the injection of 0.125 mg/kg haloperidol, but no difference after the administration of the other doses. The measurements of 3,4-dihydroxyphenylacetic acid and homovanillic acid showed a difference between the two brain structures after the injection of 0.01 mg/kg haloperidol, but did not show such a clear difference after injection of the other doses. These findings suggest that there is a difference between the anteromedial frontal cortex and the caudate putamen with respect to the regulating mechanism of dopamine release and its metabolism.

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“…One of these regions, the nucleus accumbens (Acb) in the ventral striatum is a major site where both 5-HT and dopamine modulate a variety of behaviors (Pijnenburg et al, 1976;Carter and @cock, 1977;Berger et al, 1985;Jackson et al, 1985;Nakahara et al, 1989;Geyer et al, 1990) including motivationrelated processes (Mogenson et al, 1980;Mogenson and Yang, 1991), motor function (Alheid and Heimer, 1988) and reward mechanisms (Nakahara et al, 1989). However, we previously found little morphological evidence for direct interactions between axons containing 5-HT and dopamine within the Acb (Van Bockstaele and Pickel, 1993).…”

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confidence: 97%

Pre- and postsynaptic sites for serotonin modulation of GABA-containing neurons in the shell region of the rat nucleus accumbens

1996

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The shell of the nucleus accumbens received a dense serotonergic innervation and contains abundant gamma-aminobutyric acid (GABA)-immunoreactive neurons. Moreover, serotonin (5-hydroxytryptamine: 5-HT) and GABA have been implicated in a variety of common motivational and motor-related functions partially ascribed in this brain area. We used immunoelectron microscopy of antisera directed against 5-HT and GABA in the same section of tissue to examine whether there were cellular substrates that might indicate more specific sites for functional interactions involving these transmitters in the shell region of the rat nucleus accumbens. Immunogold-silver labeling for GABA was localized to perikarya, dendrites, axons and axon terminals, whereas immunoperoxidase labeling for 5-HT was restricted to axons and axon terminals. Approximately half (187/366) of the 5-HT-immunoreactive axon terminals apposed or formed synaptic junctions with postsynaptic neurons. These junctions were mainly of the symmetric-type (83/187) characteristic of inhibitory transmitters, and were equally prevalent on dendrites with and without detectable gold-silver labeling for GABA. Of the 187 5-HT-labeled axon terminals with recognized synaptic contacts, 36% also showed convergence on a common dendrite with a GABA-labeled axon terminal. In addition, 5-HT- and GABA-immunoreactive axon terminals were commonly (83/366) identified in direct apposition to one another. Within a single plane of section, 41% of the apposed GABA-immunoreactive axon terminals formed symmetric-type junctions with dendrites or somata, whereas, the apposed 5-HT-labeled axon terminals rarely showed postsynaptic contacts. These results indicate that 5-HT-containing axon terminals may postsynaptically inhibit GABAergic neurons and their targets within the shell of the rat nucleus accumbens. Additionally, our results strongly suggest that, in this brain region, appositions between 5-HT and GABA axons and axon terminals may facilitate presynaptic interactions between these transmitter systems.

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increased dopamine and serotonin metabolism in rat nucleus accumbens produced by intracranial self-stimulation of medial forebrain bundle as measured by in vivo microdialysis

Cited by 90 publications

References 16 publications

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

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

Differential Effect of Haloperidol on Dopamine Release and Metabolism in Caudate Putamen and Anteromedial Frontal Cortex Using Intracerebral Dialysis

Pre- and postsynaptic sites for serotonin modulation of GABA-containing neurons in the shell region of the rat nucleus accumbens

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