Brain Dopamine and Serotonin Receptor Sites Revealed by Digital Subtraction Autoradiography

Altar, C. Anthony; O’Neil, Steven V.; Walter, R.J.; Jc, Marshall

doi:10.1126/science.2580352

Cited by 105 publications

(32 citation statements)

References 26 publications

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“…Importantly, the images of specific binding derived from chloroform-or non-chloroform-treated sections show similar patterns of [3H]spiroperidol binding (Fig. 3 C and D (6,(19)(20)(21) or thin sections of rat striatum (8,9,(15)(16)(17) (e.g., internal capsule). Because this fiber bundle makes up a significant proportion of the volume of the sections, the estimated Bmax will be low.…”

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confidence: 71%

“…(8)(9)(10)(15)(16)(17). Briefly, coronal sections 20 ,um thick were cut at -15°C in a cryostat and thaw-mounted onto gelatin-coated glass slides.…”

Section: Introductionmentioning

confidence: 99%

“…Circumscribed zones poor in AcChoE staining ("striosomes") are observed against a darker matrix and are coincident with other neurochemical, afferent terminal, and efferent neuron compartments (14). (8)(9)(10)(15)(16)(17). Briefly, coronal sections 20 ,um thick were cut at -15°C in a cryostat and thaw-mounted onto gelatin-coated glass slides.…”

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confidence: 99%

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Human striatal dopamine receptors are organized in compartments.

Joyce¹,

Sapp²,

Marshall³

1986

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

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Dopamine (D2) receptors visualized in postmortem human striatum by quantitative autoradiography of [3H]spiroperidol binding are organized into circumscribed zones of low receptor density separated from other such zones by regions of higher D2 density. The D2-rich zones of the caudate nucleus and putamen contain twice the binding of D2-poor zones. The Hill coefficient, obtained from saturation analysis of [3H]spiroperidol binding to thin sections of human striatum, gave a value near unity, indicating the binding was occurring to a single type of site. The patchiness of [3H]spiroperidol binding was unaltered by postincubation removal of lipid from the tissue sections, indicating that a differential absorption of tritium in white and grey matter does not account for the heterogeneous distribution. The D2-rich and D2-poor regions appear to form labyrinths oriented in the anterior-posterior axis and are typically aligned with, respectively, acetylcholinesterase-rich and -poor compartments as visualized on stained adjacent sections. Thus, the distribution of dopamine D2 receptors conforms to the "striosomal" organization of the human caudate-putamen, a finding that suggests that this receptor subtype may mediate the influence of dopamine on distinct neurochemical compartments within the structure. The brain transmitter dopamine has profound effects on mammalian movement and sensorimotor coordination. The massive ascending projections of the ventral midbrain dopaminergic neurons have been well characterized, and strong evidence points to a critical role of this system in several major neurological disorders. Abnormalities of dopaminergic transmission in human brain contribute to Parkinson disease, drug-induced dyskinetic reactions, and the cognitive disturbances of acute psychotic states (1-3). The D2 receptor (4) appears to be the principal site of action of dopamine receptor agonists and antagonists on behavior of humans and animals (5, 6). An understanding of how the D2 receptor contributes to the diversity of dopaminergic influences in the human necessitates that the distribution of these sites be determined with a high degree of anatomical resolution. This has been achieved though the application of the autoradiographic approach for the visualization of dopamine D2 receptors (7) and of computer-assisted quantitative autoradiography (8).In the rodent striatum, a sharp lateral-to-medial gradient of D2 receptors has been observed (8, 9) that appears to correspond to a similar gradient of markers for acetylcholine (AcCho) nerve terminal density (10). (8)(9)(10)(15)(16)(17). Briefly, coronal sections 20 ,um thick were cut at -15°C in a cryostat and thaw-mounted onto gelatin-coated glass slides. Immediately prior to incubation with radioligands, the sections were thawed and dried at room temperature, then transferred to glass dishes containing the preincubation buffer (50 mM Tris HCl, pH 7.1/120 mM NaCl/5 mM KCl/2 mM CaCl2/1 mM MgCl2/1 mM ascorbic acid) for 5 min at 22°C. Then Computer-Assisted Image Analysis...

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confidence: 71%

“…(8)(9)(10)(15)(16)(17). Briefly, coronal sections 20 ,um thick were cut at -15°C in a cryostat and thaw-mounted onto gelatin-coated glass slides.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human striatal dopamine receptors are organized in compartments.

Joyce¹,

Sapp²,

Marshall³

1986

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

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“…These two types of receptors represent distinct molecular entities (Nielsen et al 1984), and different distribution in the brain (Altar et al 1985;Martres et al 1985).…”

Section: Discussionmentioning

confidence: 99%

Effects of Lead Exposure on Licking and Yawning Behaviour in Rats

Ghazi‐Khansari

Rezvani

Bani‐Assadi

et al. 1998

Pharmacology & Toxicology

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Abstract:In the present study, effects of lead exposure on licking and yawning behaviour have been studied. The dopaminergic receptor agonist, apomorphine (0.15, 0.25 and 0.5 mgikg), induced dose-dependent licking in rats. The maximum response was obtained with 0.5 mgikg of the apomorphine. Lead acetate (0.05%) exposure significantly increased apomorphine-induced licking. Yawning induced by the D2 dopaminergic agonist, bromocriptine (2, 3, 4, 8 mgikg), and the cholinergic drug, physostigmine (0.1 or 0.3 mg/kg), was significantly decreased by lead acetate (0.05%) exposure. It may be concluded that the behaviour induced by dopaminergic or cholinergic agents can be affected by lead subchronic exposure.The yawning behaviour is a strange and poorly understood response induced in many vertebrate species (Baenninger 1987) Mesolimbic and nigrostriatal dopaminergic pathway may be important in the mediation of locomotor activity and stereotyped behaviours. Locomotion has been related to nucleus accumbens (Jackson et al. 1975), whereas stereotyped behaviours (e.g. head movement, licking and localized sniffing) are more closely associated with the caudatestriatum (Kelly et al. 1975).Lead exposure is still one of the most important health hazards to human, and in particular to children as due to their enhanced sensitivity of developing nervous system, they are more susceptible to lead exposure (Mushak et al. 1989). Lead exposure has been reported in animal experiments (Murayama et al. 1990). It has also been shown that lead is capable of affecting dopamine receptor subtypes (Moresco et al. 1988). Further, lead exposure also has been found to produce functional dopaminergic supersensitivity which involves both the D, and D2 receptor subtypes behaviour, the present study was undertaken to investigate the effects of lead exposure on yawning and licking behaviour induced by dopaminergic and cholinergic agents. Materials and MethodsAnimals. Male albino wistar rats (1 50-250 g; 3 4 months old) were used for all experiments. Prior to use the rats were housed in wire cages in groups of five, with controlled temperature (20+2") and controlled 12 hr light-dark cycle. The animals were allowed ad libitum access to a standard cube diet and water.Lead exposure. Lead was administered according to Moorhouse et al. (1988) with minor modification. In brief, lead was placed in drinking water (acetate form dissolved in distilled water acidified with hydrochloric acid to prevent precipitation of insoluble lead salts). Glucose (5% w/v) was added to each water bottle to improve palatability. Two doses of lead (0.025% and 0.05%) were used in this study and control groups were treated with a corresponding solution of sodium acetate. Similar quantities of acid and glucose were added to the drinking water of the sodium acetate control animals. Animals were divided in 5 groups: the first two groups of animals received lead or sodium acetate for 28 days and licking and yawning behaviour induced by different doses of apomorphine or bromocriptine were tes...

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“…The D 1 dopamine receptor is positively coupled to adenylate cyclase, which stimulates the production of CAMP (Kebabian and Calne, 1979) while the D2 dopamine receptor is negatively coupled to adenylate cyclase and inhibits the formation of CAMP (Onali et al, 1984;Stoof and Kebabian, 198 1). Both Dl and D2 receptors are present in the mesolimbic and striatal brain regions (Altar et al, 1985;Dawson et al, 1985;Miller et al, 1974;Ryan Jastrow et al, 1984;Schulz et al, 1984). Thus, because dopamine may stimulate receptors having functionally antithetical effects, it is important to be able to dissociate these receptor subtypes when evaluating treatments that affect dopaminergic neurotransmission.…”

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Differential down-regulation of D1-stimulated adenylate cyclase activity in rat forebrain after in vivo amphetamine treatments

Roberts-Lewis¹,

Ph²,

Iwaniec³

et al. 1986

J. Neurosci.

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Amphetamine has complex behavioral actions in the rat that depend upon the release of dopamine in striatal and mesolimbic brain regions. To explore a possible role of the dopamine-sensitive CAMP second-messenger system in mediating these effects, we examined the effects of in viva amphetamine treatments on the Dl receptor-coupled adenylate cyclase system in membranes from striatal and mesolimbic rat brain regions. The results show that amphetamine produces a regional, dose-and time-dependent down-regulation of adenylate cyclase activity. Intermediate and high doses of amphetamine (2.5 and 7.5 mg/kg, respectively), but not a low dose (1.0 mg/kg), resulted in a decrease in the apparent Vmx and/or an increase in the apparent K. for the selective Dl partial agonist, SKF38393, in striatal membranes 30 min after amphetamine treatment. Treatment of rats with 7.5 mg/kg amphetamine for 30 and 60 min, but not 10 min, similarly resulted in a down-regulation of Dl-mediated adenylate cyclase activity in striatal membranes. In contrast, in mesolimbit tissues, no amphetamine treatment at any time resulted in an alteration of SKF38393-stimulated adenylate cyclase activity relative to saline controls. The results of behavioral analyses also showed that animals exhibiting intense stereotypies had significantly lower striatal apparent V,, values than did those animals engaged in moderate or no behavioral activity at the time of decapitation. These findings demonstrate that amphetamine treatments result in a down-regulation of striatal, but not mesolimbic, dopamine-sensitive adenylate cyclase activity that parallels the intense, stereotyped behaviors characteristic of dopaminergic activation in the striatum.Amphetamine (AMPH), a phenylethylamine derivative, is a potent CNS stimulant with a multiplicity of behavioral and physiological effects (see Tepper, 1983, andSchuckit, 1983, for reviews). At lower doses of AMPH (1 .O mg/kg), rats exhibit enhanced locomotor activity and exploratory behaviors. As the dose is increased (e.g., 2.5 mg/kg), rats begin to show episodic bouts of repetitive head and limb movements (stereotypies). After a high dose of AMPH (5-7.5 mg/ kg), a similar sequence of behaviors may be observed as a function of time after AMPH administration. Shortly after the drug injection (ca. 10 min), rats show a marked increase in rearing and sniffing, or locomotor activity, followed (ca. 30 min) by stereotyped head and limb movements. By 60 min after AMPH administration, most animals are engaged in intense, continuous stereotypy, head oriented down toward the cage floor, often accompanied by oral stereotypies such as licking or gnawing. These multiphasic time-and dose-dependent behavioral effects

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Brain Dopamine and Serotonin Receptor Sites Revealed by Digital Subtraction Autoradiography

Cited by 105 publications

References 26 publications

Human striatal dopamine receptors are organized in compartments.

Human striatal dopamine receptors are organized in compartments.

Effects of Lead Exposure on Licking and Yawning Behaviour in Rats

Differential down-regulation of D1-stimulated adenylate cyclase activity in rat forebrain after in vivo amphetamine treatments

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