Expression of D1 receptor, D2 receptor, substance P and enkephalin messenger RNAs in the neurons projecting from the nucleus accumbens

Lü, Xin; Ghasemzadeh, Mehdi; Kalivas, Peter W.

doi:10.1016/s0306-4522(97)00327-8

Cited by 264 publications

(252 citation statements)

References 73 publications

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“…The D1R antibody used in this study is well characterized by Western blot, immunoprecipitation and blocking control experiments and shows high specificities in the Acb and other brain areas known to express D1Rs (Weiner et al, 1991;Levey et al, 1993;Lu et al, 1998). Moreover, the normal localization of D1Rs in our control group (VEH) matched previous light and electron microscopic immunocytochemical studies using the same antibody (Hara and Pickel, 2005).…”

Section: Methodological Considerationssupporting

confidence: 60%

Dendritic distributions of dopamine D1 receptors in the rat nucleus accumbens are synergistically affected by startle-evoking auditory stimulation and apomorphine

Hara

Pickel

2007

Neuroscience

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Prepulse inhibition of the startle response to auditory stimulation (AS) is a measure of sensorimotor gating that is disrupted by the dopamine D1/D2 receptor agonist, apomorphine. The apomorphine effect on prepulse inhibition is ascribed in part to altered synaptic transmission in the limbicassociated shell and motor-associated core subregions of the nucleus accumbens (Acb). We used electron microscopic immunolabeling of dopamine D1 receptors (D1Rs) in the Acb shell and core to test the hypothesis that region-specific redistribution of D1Rs is a short-term consequence of AS and/or apomorphine administration. Thus, comparisons were made in the Acb of rats sacrificed one hour after receiving a single subcutaneous injection of vehicle (VEH) or apomorphine (APO) alone or in combination with startle-evoking AS (VEH+AS, APO+AS). In both regions of all animals, the D1R immunoreactivity was present in somata and large, as well as small, presumably more distal dendrites and dendritic spines. In the Acb shell, compared with the VEH+AS group, the APO+AS group had more spines containing D1R immunogold particles, and these particles were more prevalent on the plasma membranes. This suggests movement of D1Rs from distal dendrites to the plasma membrane of dendritic spines. Small-and medium-sized dendrites also showed a higher plasmalemmal density of D1R in the Acb shell of the APO+AS group compared with the APO group. In the Acb core, the APO+AS group had a higher plasmalemmal density of D1R in medium-sized dendrites compared with the APO or VEH+AS group. Also in the Acb core, D1R-labeled dendrites were significantly smaller in the VEH+AS group compared to all other groups. These results suggest that alerting stimuli and apomorphine synergistically affect distributions of D1R in Acb shell and core. Thus adaptations in D1R distribution may contribute to sensorimotor gating deficits that can be induced acutely by apomorphine or develop over time in schizophrenia.

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Section: Methodological Considerationssupporting

confidence: 60%

Dendritic distributions of dopamine D1 receptors in the rat nucleus accumbens are synergistically affected by startle-evoking auditory stimulation and apomorphine

Hara

Pickel

2007

Neuroscience

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“…At least a portion of these neurons projects to the VTA (Lu et al, 1998). Thus, psychostimulants activate this direct pathway, causing the release of GABA as well as substance P and dynorphin in the VTA.…”

Section: Discussionmentioning

confidence: 99%

“…Substance P/dynorphin-containing MSNs in the NAc shell project to the VTA (Lu et al, 1998) and psychostimulant administration also increases dynorphin peptide levels in the midbrain (You et al, 1994;Bustamante et al, 2002). Therefore, we investigated whether amphetamine alters KOP receptor function in the VTA.…”

Section: Kop Receptor Function In the Vtamentioning

confidence: 99%

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Xia

Whistler

et al. 2007

Neuropsychopharmacol

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In the present study, we investigated the effects of psychostimulant exposure on k-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, s.c.) and dynorphin (1 mM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline-or amphetaminetreated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.

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“…GABAergic enkephalinergic neurons contain dopamine and adenosine receptors predominantly of the D 2 and A 2A subtype, respectively. On the other hand, GABAergic dynorphinergic neurons express A 1 and D 1 receptors predominantly (Robertson and Jian, 1995;Ferré, 1997;Svenningsson et al, 1997a;Lu et al, 1998). In the ventral striatum GABAergic enkephalinergic and dynorphinergic cells project to the ventral pallidum, which is considered to be an output structure of the basal ganglia (reviewed in Ferré, 1997).…”

Section: Adenosine a 2a Receptors In The Ventral Striatum And The Acumentioning

confidence: 99%

“…The nucleus accumbens also projects to the ventral mesencephalon, with the shell innervating the VTA and the core innervating the substantia nigra. These accumbens-mesencephalic projections are mostly represented by GABAergic dynorphinergic neurons (Robertson and Jian, 1995;Ferré, 1997;Svenningsson et al, 1997a;Lu et al, 1998).…”

Section: Adenosine a 2a Receptors In The Ventral Striatum And The Acumentioning

confidence: 99%

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

128

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Adenosine A 2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A 2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A 2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A 2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A 2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A 2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A 1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A 2A receptors. A 2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A 1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A 2A receptor knockout mice suggest that A 2A receptor antagonists might have some therapeutic potential in pain states, in particular where high intensity stimuli are prevalent.

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Expression of D1 receptor, D2 receptor, substance P and enkephalin messenger RNAs in the neurons projecting from the nucleus accumbens

Cited by 264 publications

References 73 publications

Dendritic distributions of dopamine D1 receptors in the rat nucleus accumbens are synergistically affected by startle-evoking auditory stimulation and apomorphine

Dendritic distributions of dopamine D1 receptors in the rat nucleus accumbens are synergistically affected by startle-evoking auditory stimulation and apomorphine

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

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