The dopamine D3 receptor and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232; a microdialysis study

Waters, Nicholas; Lagerkvist, Sören; Löfberg, Lena; Piercey, Montford F.; Carlsson, Arvid

doi:10.1016/0014-2999(93)90075-s

Cited by 80 publications

(42 citation statements)

References 50 publications

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“…Lower doses have been reported to inhibit motor activity in rats, due to a preferential action either at presynaptic D 2 -like autoreceptors that attenuate endogenous DAergic activity, or at a putative population of postsynaptic D 2 -like receptors that exert an inhibitory role on DA-mediated function (Waters et al, 1993;; such a profile may be less evident in mice and the present studies utilized only a single low dose, so as to accommodate also higher, stimulatory doses, following habituation to optimize the resolution of stimulatory effects . However, it was notable that relative to wildtypes, low-dose apomorphine in DARPP-32 mutants was associated with reduced levels of sniffing, total grooming, total rearing, and rearing seated, with higher levels of stillness.…”

Section: Discussionmentioning

confidence: 99%

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 ‘Knockout’

Nally

McNamara

Clifford

et al. 2003

Neuropsychopharmacol

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Congenic (10 backcrosses into C57BL/6J) mutants with targeted gene deletion of DARPP-32, a neuronal phosphoprotein regarded as an essential mediator of the biological effects of dopamine (DA), were assessed phenotypically using an ethologically based approach that resolves all topographies of behavior in the mouse repertoire. Over initial exploration, female, but not male, DARPP-32 mutants evidenced increased locomotion and decreased grooming, while a decrease in rearing seated was evident in mutants of both genders; continuing assessment over several hours did not reveal additional phenotypic effects. Following challenge with the nonselective DA receptor agonist apomorphine, low doses were associated with reduced levels of sniffing, grooming, total rearing, and rearing seated in DARPP-32 mutants relative to wildtypes; this would suggest some role for DARPP-32 in mediating the biological effects of presynaptic D 2 -like autoreceptor or inhibitory postsynaptic D 2 -like receptor activation. Following challenge with higher doses, while stereotyped sniffing and locomotion with chewing was largely unaltered, the additional murine response of Straub tail was essentially abolished in DARPP-32 mutants, indicating some specific involvement of DARPP-32 in mediating this topography of behavior; additionally, there were overall reductions in levels of sniffing, total rearing, rearing seated, and grooming in DARPP-32 mutants that were unrelated to the dose of apomorphine administered, indicating broader topographical effects following the stress of the injection procedure relative to more naturalistic conditions. The developmental absence of DARPP-32 following targeted gene deletion appears to be associated with compensatory processes that maintain certain topographies of spontaneous and agonist-induced DAergic function, while other topographies remain impaired.

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Section: Discussionmentioning

confidence: 99%

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 ‘Knockout’

Nally

McNamara

Clifford

et al. 2003

Neuropsychopharmacol

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“…The levels of DOPA were measured with standard HPLC-EC techniques. Dialysis experiments were performed in awake and freely moving rats as described by Waters et al (1993b).…”

Section: Methodsmentioning

confidence: 99%

Locomotor inhibition by the D3 ligand R-(+)-7-OH-DPAT is independent of changes in dopamine release

Svensson

Carlsson

Waters

1994

J. Neural Transmission

126

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“…The in vivo microdialysis was performed essentially as described by Waters et al (1993) (dopamine) and Tao and Hjorth (1992) (serotonin). For the analysis of dopamine release in the nucleus accumbens and the striatum, an I-shaped probe was used (Santiago and Westerink, 1990), whereas, for the investigation of serotonin release in hippocampus, the probe used was U-shaped (Tao and Hjorth, 1992).…”

Section: In Vivo Microdialysis/high-performance Liquid Chromatographymentioning

confidence: 99%

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Eriksson

Engberg²,

Bing³

et al. 1999

Neuropsychopharmacology

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Intravenous administration of m-chloro-phenylpiperazine (mCPP) (0.25 or 2.5 mg/kg) induced a marked and doserelated increase in extracellular concentrations of serotonin in hippocampus (300-1,400% of baseline) as measured using in vivo microdialysis in awake male Wistar rats of the spontaneously hypertensive (SH) strain. Indicating that the effect of mCPP was caused by a reversal of the serotonin transporter, it was antagonized by pretreatment with the serotonin re-uptake inhibitor citalopram (10 mg/kg) but was unaffected by local administration of the sodium channel blocker tetrodotoxin (TTX; 1 m). mCPP was also shown to induce an increase in extracellular concentrations of dopamine in the nucleus accumbens and the striatum of SH rats and in the nucleus accumbens of rats of the Sprague-Dawley (SD) Dopamine, In vivo microdialysis; Hippocampus; Striatum, Nucleus accumbens; Citalopram; Rat m-Chloro-phenylpiperazine (mCPP), the metabolite of the antidepressant drug trazodone, has recently gained marked attention as a putative probe of serotonergic function in clinical psychiatric research. Thus, the prolactin, ACTH, and cortisol responses to mCPP frequently have been used as putative markers of postsynaptic serotonin receptor function in various psychiatric disorders. Moreover, administration of mCPP has been shown to elicit, and/or aggravate, anxiety attacks in patients with panic disorder, obsessions in patients with obsessive compulsive disorder (OCD), elation in alcoholics and cocaine addicts, and positive symptoms in schizophrenic patients (see Murphy et al. 1991;Kahn and Wetzler 1991;Krystal et al. 1993;Buydens-Branchey et al. 1993;Krystal et al. 1994).mCPP displays high affinity to 5-HT2C receptors and moderate, or low, affinity to 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT3 receptors; in addition, the compound has some affinity for alpha-2-adrenoceptors. At the 5-HT2C receptor, mCPP seems to act as a partial agonist with relatively high intrinsic efficacy, whereas, at the other serotonin receptors, the intrinsic efficacy of mCPP is moderate or low (see Murphy et al. 1991 NO . 3 and Wetzler 1991). The behavioral and endocrine effects of mCPP observed in clinical studies are generally attributed to the direct effects of mCPP on various subtypes of serotonin receptors; in contrast, little attention has been paid to the report by Baumann et al. (1993) suggesting that mCPP may also stimulate serotonin release by means of an interaction with the serotonin transporter (see also Baumann et al. 1995).To further elucidate the possible influence of mCPP on the release of serotonin, we studied the effects of a high dose of mCPP on extracellular, hippocampal concentrations of serotonin in awake, freely moving rats using in vivo microdialysis.Enhanced dopaminergic neurotransmission has been suggested as a mechanism of importance both for the positive symptoms of schizophrenia and for the euphoria induced by such central stimulants as cocaine. The observations that mCPP may aggravate psychotic symptoms in schizophr...

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The dopamine D3 receptor and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232; a microdialysis study

Cited by 80 publications

References 50 publications

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 ‘Knockout’

Topographical Assessment of Ethological and Dopamine Receptor Agonist-Induced Behavioral Phenotype in Mutants with Congenic DARPP-32 ‘Knockout’

Locomotor inhibition by the D3 ligand R-(+)-7-OH-DPAT is independent of changes in dopamine release

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

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