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At least 1,207 records · Page 67Linked to original sources
PubMed2000

Degree of immediate early gene induction in striatum by eticlopride determines sensitivity to N-methyl-D-aspartate receptor blockade.

Cortical afferents excite striatal efferent neurons through activation of N-methyl-D-aspartate (NMDA) receptors, which can be modulated by D2 dopamine receptors. It is suggested that activation of PKA by D2 receptor blockade leads to NMDA receptor phosphorylation in the dendrites or phosphorylation of transcription factors in the nucleus. Thus, the levels and cellular localization of activated PKA may determine if D2 antagonist-mediated gene expression is dependent on NMDA receptor activation. We have previously demonstrated that NMDA receptor antagonists block gene expression induced by a high dose of eticlopride in medial and central but not lateral striatum. Here, we examined the effects of NMDA receptor antagonists on striatal gene expression after administration of a low dose of eticlopride. The results showed that NMDA receptor antagonists blocked gene induction by eticlopride throughout striatum. Less PKA activation by the low dose of eticlopride might explain why the expression was more sensitive in the lateral striatum to NMDA receptor blockade than in our previous study. To increase levels of PKA activation to the extent that NMDA receptor blockade would have less effect on eticlopride-mediated gene induction in all regions of striatum, we administered the phosphodiesterase inhibitor IBMX to animals treated with eticlopride. The combined administration of IBMX and eticlopride induced gene expression that was only partially attenuated (c-fos) or unaffected (zif268) by NMDA receptor blockade. These data support the suggestion that the degree of second messenger activation by D2 receptor blockade determines whether D2 dopamine receptor antagonist-mediated gene expression is dependent on NMDA receptor activation.

1-Methyl-3-isobutylxanthine↗
PubMed2003

Dopamine effect on the stimulus pattern related changes in response characteristics of R/G horizontal cells in carp retina.

Repetitive red flashes increased the R/G horizontal cells' red response amplitude and induced a hyperpolarization of the cells' dark membrane potential. These phenomena were eliminated in 6-OHDA pretreated retinas and restored by exogenous dopamine, which suggests the involvement of dopamine receptor activity changes instead of dopamine release changes. Furthermore, the phenomena persisted on D(1) receptor antagonist (SKF-83566) application, whereas they diminished on D(2) receptor antagonist (eticlopride) application, indicating that the mechanism is related to a D(2) receptor, possibly located on photoreceptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

D2 dopamine receptor activation inhibits basal and forskolin-evoked acetylcholine release from dissociated striatal cholinergic interneurons.

We tested whether D2 ligands inhibit basal and forskolin-stimulated [3H]ACh release from dissociated striata, as opposed to striatal slices. Quinpirole inhibited both basal (40% maximal inhibition; IC50 approximately 50 nM) and 10 microM forskolin-stimulated release (80% inhibition; IC50 approximately 25 nM quinpirole) and both actions were blocked by a D2 antagonist. Vesamicol prevented the quinpirole and forskolin actions. The ability of D2 agonists to inhibit basal and cyclase-stimulated acetylcholine release emanating from vesamicol-sensitive vesicles appears to be tonically suppressed by inhibitory elements within striatal circuitry.

Acetylcholine↗
PubMed1997

The involvement of dopamine D2 receptors, but not D3 or D4 receptors, in the rewarding effect of brain stimulation in the rat.

To identify the subtype of dopamine receptors critically involved in the rewarding effect of brain stimulation, four dopamine antagonists were intracranially injected in 25 rats. The importance of dopamine D1 receptors had been demonstrated previously by using SCH 23390, a highly selective D1 antagonist. Rats were implanted with electrodes into the medial forebrain bundle and cannulae into either one of the following structures: the nucleus accumbens, the vicinity of the islands of Calleja, or the ventral tegmental area, all ipsilateral to the electrodes. The animals were trained to press a bar for electrical stimulation, and the frequency-response functions were plotted before and after injection of each dopamine antagonist through the cannulae. Raclopride and haloperidol, which have high affinities for D2 receptors, reduced the rewarding effect after injection into any one of the three cannula sites. Neither (+)-UH232, a selective D3 antagonist, nor clozapine, a D4 antagonist, influenced the rewarding effect. The results suggest that dopamine D2, but not D3 or D4, receptors are critically involved in producing the rewarding effect of brain stimulation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Differential labeling of dopamine and sigma sites by [3H]nemonapride and [3H]raclopride in postmortem human brains.

The difference between the binding of [3H]nemonapride and [3H]raclopride has been used to quantify dopamine D4 receptors in postmortem schizophrenic brain studies. Recent work, however, has suggested that at least part of the differential between [3H]nemonapride and [3H]raclopride binding may represent sigma rather than D4 receptor sites. We applied the nemonapride-raclopride subtraction method to postmortem, non-schizophrenic human striatum to examine the variation in dopaminergic receptor binding labeled by these ligands. Variation in sigma receptor binding labeled by [3H]nemonapride was studied in frontal cortex, striatum and cerebellum. Specific binding was defined by sulpiride (dopamine receptor ligand), PPAP (sigma receptor ligand) and haloperidol (mixed dopaminergic/sigma agent), respectively. Haloperidol defined a combination of sites, which were approximately the sum of the dopaminergic and sigma components defined by sulpiride and PPAP, respectively. Significant inter-individual variation in the amount of specific binding for dopaminergic and sigma receptor sites was observed. However, no significant nor consistent observation of striatal dopamine D4 receptors or D4-like binding sites was observed in the striatum even though two independent sets of tissues, with different dissections were used. The inconsistencies in some previous postmortem studies appear to be at least partially explained by the inclusion of both sigma and dopaminergic components in [3H]nemonapride binding and the inherent high inter-individual variability of the different components.

Adult↗
PubMed1997

Dopamine D1- and D2-dependent catalepsy in the rat requires functional NMDA receptors in the corpus striatum, nucleus accumbens and substantia nigra pars reticulata.

This study investigated the anticataleptic activity of MK-801 versus the D1 antagonist SCH 23390 and the D2 antagonist raclopride, using the horizontal bar test in the rat. MK-801, 0.2 mg/kg i.p., strongly opposed the cataleptogenic actions of SCH 23390 and raclopride administered systemically (1 and 3 mg/kg i.p., respectively), or directly into the corpus striatum (CS) or nucleus accumbens (NAc; 1 and 10 microg, respectively). Conversely, intraCS and intraNAc pretreatment with MK-801 (10 microg) markedly attenuated the cataleptic response to a systemic injection of SCH 23390 or raclopride. In the latter experiments the anticataleptic effect of MK-801 was pronounced and sustained (> 2 h), except with intraCS MK-801 versus raclopride, where it was initially profound but only short-lived (15 min). Stereotaxic injection of MK-801 (1 microg) into the substantia nigra pars reticulata (SNr) prevented catalepsy developing to either dopamine D1 or D2 receptor antagonism. These results indicate there must be unimpeded glutamate neurotransmission in the CS and NAc before catalepsy can develop fully to D1 and D2 dopamine receptor blockade in these structures. The weaker glutamate-D2 interaction in the CS than in the NAc may be related to differences in the N-methyl-D-aspartate receptor subpopulations in these nuclei. Finally, the ability of intranigral MK-801 to diminish both D1- and D2-dependent catalepsy suggests the SNr acts as a common output pathway for the expression of both forms of catalepsy in the rat.

Animals↗
PubMed1997

Dopamine receptor-mediated regulation of expression of Fos and its related antigens (FRA) in somatostatin neurons in the hypothalamic periventricular nucleus.

Somatostatin (SS)-containing perikarya located within the hypothalamic periventricular nucleus (PeVN) comprise a heterogenous population of neurons with both local intrahypothalamic and distant extrahypothalamic axonal projection sites. The close proximity of SS perikarya and their dendrites to dopaminergic (DA) neuronal processes in the PeVN suggests that these peptidergic neurons may be regulated by DA receptor-mediated mechanisms. To test this, the effects of the D1 agonist SKF 38393 and D2/3 agonist quinelorane were examined on expression of the immediate early gene products Fos and its related antigens (FRA) in SS-immunoreactive (IR) neurons in the PeVN. SS-IR neurons were located in the most medial portion of the PeVN bordered medially by the third ventricle and laterally by tyrosine hydroxylase (TH)-IR neurons. In control rats, 10-15% of all SS-IR neurons contained FRA-IR. Activation of D1 receptors with SKF 38393 had no effect on either the total number of SS-IR neurons or the number of SS-IR neurons containing FRA-IR. In contrast, activation of D2/3 receptors with quinelorane decreased the number of SS-IR neurons containing FRA-IR, without affecting the total number of SS-IR neurons. The D2/3 antagonist raclopride had no effect per se, but prevented the quinelorane-induced decrease in the number of SS neurons expressing FRA-IR. These results reveal that activation of D2/3 (but not D1) receptors inhibits expression of the immediate early gene products FRA in SS-containing neurons in the PeVN, but expression of FRA in SS neurons is not tonically inhibited by dopamine acting on D2/3 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Quantitative autoradiographic studies of dopamine D3 receptors in rat cerebellum using [125I]S(-)5-OH-PIPAT.

Recently, [125I]S(-)5-OH-PIPAT (5-hydroxy-2-(N-n-propyl-N-3'-iodo-2'-propenyl)amino-tetralin) was reported to be a selective radioiodinated ligand for dopamine D2-like receptors. This ligand displayed a high binding affinity (Kd = 0.3-0.4 nM) and an agonist binding profile to dopamine D2 and D3 receptors expressed in HEK293 cells and dopamine D4 receptors expressed in CHO cells. Herein, a series of studies to characterize D3 receptors in native tissues is presented. Based on studies of the distribution of receptor mRNA, D3, but not D2, receptors are present in the rat cerebellum. Quantitative autoradiographic experiments using [125I]S(-)5-OH-PIPAT to label molecular layers 9 and 10 of rat cerebellum were conducted. Saturation experiments demonstrated that [125I]S(-)5-OH-PIPAT bound with high affinity (Kd = 0.1 nM) to a low density (approximately 3 fmol/mg protein) of sites in molecular layers 9 and 10 of rat cerebellum. Increasing concentrations of Gpp(NH)p, but not ATP, decreased the specific binding of [125I]S(-)5-OH-PIPAT in rat cerebellum slices. In comparison studies, binding of [125I]NCQ298, a dopamine D2/D3 receptor antagonist, with a similar affinity (Kd = 0.2 nM) for D3 receptors as [125]S(-)5-OH-PIPAT, was not sensitive to Gpp(NH)p. Analysis of inhibition by S(-)5-OH-PIPAT of [125I]NCQ298 binding to rat cerebellum resulted in two-site binding with IC50 values of 0.07 nM and 6.0 nM. In the presence of GTP (300 microM), the data best fit a one-site model with an IC50 value of 1.6 nM. Agonists and antagonists inhibited the binding of [125I]S(-)5-OH-PIPAT in the cerebellum with a rank order of potency consistent with an interaction at D3 receptors. These results indicate that [125I]S(-)5-OH-PIPAT binds to D3 receptors in rat cerebellum. Furthermore, [125I]S(-)5-OH-PIPAT binds to GTP sensitive and GTP insensitive states of D3 receptors with distinctive high and low affinity states, respectively.

Animals↗
PubMed1998

Methamphetamine-induced alterations in dopamine transporter function.

Repeated methamphetamine (METH) administration has been shown to produce differing neurochemical as well as behavioral effects in rats. This study was designed to examine the effects of acute and chronic METH exposure on uptake and release of [3H]dopamine (DA) in cultured midbrain dopamine neurons to determine if persistent neuronal adaptations ensue. In addition, we have assessed DA D2 receptor function to determine if chronic METH alters this receptor. Fetal midbrain cultures were exposed to METH (1, 10 microM) for 5 days and dopaminergic function examined 1 or 7 days after drug removal. The ability of METH to release [3H]DA was compared to other releasing agents as well as several potent uptake inhibitors. Chronic exposure to a release-promoting concentration of METH resulted in either no change or a reduction in [3H]DA release upon subsequent METH challenge. Pretreatment with METH was also found to cause a decrease in the Bmax for [3H]raclopride binding, suggesting that persistently elevated DA levels cause a downregulation of DA D2 receptors. Examination of transporter kinetics utilizing initial velocity of uptake revealed that METH treatment caused a significant decrease in affinity (K(m)) for the substrate (DA), while not altering the maximal velocity of uptake (Vmax). Binding studies with [125I]RTI-55 revealed that there was no alteration in either the Bmax or Kd for this ligand, suggesting that the changes induced by METH treatment are due to alterations in K(m) and not in the number of DA transport sites. The results from these studies indicate that METH treatment produces a modification in transporter function which may be associated with both the altered uptake and release of [3H]DA. These changes have broad implications for the regulation of transporter activity not only because of the relevance to pre-synaptic mechanisms controlling neurotransmission, but also to the importance of the neuronal adaptation that occurs in response to chronic METH exposure.

Animals↗
PubMed1998

Dopaminergic agonists administered into the nucleus accumbens: effects on extracellular glutamate and on locomotor activity.

The hypothesis to be tested was that increased dopaminergic transmission induced by amphetamine in the nucleus accumbens results in increased glutamatergic neurotransmission in this brain area and that the increase in level of this neurotransmitter contributes to behavioral effects of psychostimulant drugs. Amphetamine (1 mg/kg, i. p.) increased the amount of extracellular glutamate in the accumbens, as measured by in vivo dialysis, and stimulated locomotor activity. Amphetamine (10 mM) infused into the accumbens by reverse dialysis through the probe produced a similar stimulation of locomotor activity as systemic amphetamine but a greater increase in extracellular glutamate levels. Both of these responses to amphetamine were attenuated by either the selective D1 antagonist SCH23390 or the selective D2 antagonist eticlopride. The combination of a D1 and D2 agonist, SKF38393 (20 mM) and quinpirole (50 mM), administered into the accumbens by reverse dialysis also increased extracellular glutamate and stimulated locomotor activity. Administration of a glutamate uptake inhibitor, threo-beta-hydroxy-aspartate (50 mM), increased extracellular glutamate but did not stimulate locomotor activity. Systemic administration of caffeine (15 mg/kg, i.p.) increased locomotor activity but did not increase extracellular levels of glutamate. These data suggest that activation of dopaminergic receptors in the nucleus accumbens results in stimulation of locomotor activity and in activation of glutamatergic transmission in this brain region. However, an increase in glutamate levels in the nucleus accumbens is neither sufficient nor necessary to produce a stimulation of locomotor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Age-related alteration of the adenosine/dopamine balance in the rat striatum.

An antagonistic interaction between adenosine A2A- and dopamine D2-receptors has been described. Radioligand binding experiments showed a predominant reduction in the number of D2 vs. A2A-receptors in the striatum of aged compared to young rats. The A2A-receptor-mediated antagonistic modulation of D2-receptor binding remained unchanged in aged animals. In striatal homogenates a significant increase in adenosine and no change in dopamine content was found in aged vs. young rats. These results reveal the existence of an age-dependent imbalance of adenosine vs. dopamine in favor of adenosine, which involves both presynaptic and postsynaptic mechanisms.

Adenosine↗
PubMed1998

Methamphetamine induces fos expression in the striatum and the substantia nigra pars reticulata in a rat model of Parkinson's disease.

In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion in the nigrostriatal pathway, methamphetamine (3 mg/kg, i.p.) induced Fos-like immunoreactivity (FLI) not only in the striatum on the intact side but also in the substantia nigra pars reticulata (SNr) on the lesioned side. The methamphetamine-induced hyperexpression of FLI in the SNr on the lesioned side was suppressed by pretreatment with either dopamine D1 receptor antagonist SCH-23390 (0.5 mg/kg, i.p.), D2 receptor antagonist raclopride (2 mg/kg, i.p.) or N-methyl-d-aspartate receptor antagonist MK-801 (1 mg/kg, i.p.), which was concomitant with inhibition of the methamphetamine-induced rotational behavior of each antagonist. However, the hyperexpression of FLI in the SNr was not suppressed by intrastriatal grafts of fetal ventral mesencephalon which could suppress the methamphetamine-induced rotation completely. These results indicate that opposite hemispheric asymmetries in FLI are induced by methamphetamine in the striatum and the SNr in the 6-OHDA rats. It is suggested that the FLIs in the two discrete sites are activated independently by different mechanisms, and furthermore, different neuronal pathways are involved in the methamphetamine-induced rotation and Fos expression in the SNr of 6-OHDA rats.

Animals↗
PubMed1999

Partial antagonism of 8-OH-DPAT'S effects on male rat sexual behavior with a D2, but not a 5-HT1A, antagonist.

The serotonin agonist 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), injected systemically or directly into the medial preoptic area (MPOA), reduces the ejaculatory threshold in male rats. While 8-OH-DPAT has been characterized as an agonist at the 5-HT1A receptor, it also acts at other receptor sites including the dopamine D2 receptor. The current experiments investigated whether 8-OH-DPAT injected into the MPOA facilitates male sexual behavior through stimulation of the 5-HT1A receptor or the dopamine D2 receptor. Experiment 1 co-administered 8-OH-DPAT (6 microgram) with either the 5-HT1A antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-ben zamide hydrochloride (MPPI) (10 microgram) or the D2 antagonist raclopride (10 microgram). Raclopride blocked 8-OH-DPAT's facilitative effects on ejaculation frequency and latency, while the 5-HT1A antagonist was ineffective. In Experiment 2, 8-OH-DPAT (500 microM), retrodialyzed into the MPOA through a microdialysis probe, enhanced male copulatory behavior similarly to the microinjection, increasing ejaculation frequency and decreasing ejaculation latency, postejaculatory interval and mount frequency. Retrodialyzing 8-OH-DPAT through a microdialysis probe in the MPOA had been previously shown to increase extracellular levels of dopamine and serotonin. The data from the present studies suggest that the effects of 8-OH-DPAT in the MPOA on male rat copulatory behavior may be mediated, at least in part, either directly through 8-OH-DPAT's activity at D2 receptors or indirectly through 8-OH-DPAT's ability to increase extracellular dopamine.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Dopaminergic modulation of pallidal preproenkephalin mRNA.

The present study examines dopaminergic regulation of neuropeptide gene expression within a relatively poorly characterized population of cells, the preproenkephalin (PPE) mRNA containing neurons of the globus pallidus (GP). Rats that received 6-hydroxydopamine (6-OHDA) lesions or repeated D1 or D2 antagonist administration were compared to control animals. One month after 6-OHDA lesions, PPE mRNA was elevated in the GP ipsilateral to the lesion, with a smaller elevation also being observed in the contralateral GP. Repeated administration of eticlopride, but not SCH 23390, also resulted in elevated PPE mRNA expression in the GP. These data reveal a novel effect of decreased dopamine transmission on the GP, and draw attention to this subpopulation of pallidal neurons.

Animals↗
PubMed2000

Rats sensitized to morphine are resistant to the behavioral effects of an unavoidable stress.

In agreement with the results of other authors, rats sensitized to morphine and challenged with 5 mg/kg of morphine after 7 days of wash-out showed intense stereotyped movements, the expression of which was selectively antagonized by SCH 23390. Sensitized rats were exposed to an unavoidable stress (which consistently produces an escape deficit in control animals) after 3, 7 and 21 days of morphine wash-out. Twenty-four hours after the unavoidable stress, animals were tested for their capacity to escape and their performance was compared to that of control-stressed and naive rats. Morphine sensitization completely prevented the development of escape deficit. This protective effect was similar to that induced by a chronic imipramine treatment and, like the effect of imipramine, it was antagonized by the administration of SCH 23390 before the unavoidable stress. However, it was not affected by the administration of naloxone. Moreover, when rats presenting a clear-cut escape deficit, induced by a 10-day treatment with SKF 38393, were exposed to the morphine sensitization protocol, a complete recovery of their capacity to avoid a noxious stimulus was observed. Finally, the down-regulation of both the number of D(1)-dopamine receptors and of the coupled adenylyl cyclase activity in the pre-frontal cortex (PFC) produced by long-term SKF 38393 administration was reverted by the superimposed morphine sensitization. Thus, the condition of morphine sensitization appears to share several common effects with chronic imipramine treatment.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2002

Phencyclidine increases vesicular dopamine uptake.

Phencyclidine (PCP) rapidly (within 1 h) increased vesicular dopamine uptake and binding of the vesicular monoamine transporter-2 (VMAT-2) ligand, dihydrotetrabenazine. Uptake returned to basal values 3 h in the striatum after a high-dose administration of this drug (15 mg/kg i.p.). In contrast, a similar pretreatment with another non-competitive NMDA receptor antagonist, dizocilpine;([5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine; MK-801; 1 mg/kg, i.p.), was without effect on vesicular dopamine uptake. Pretreatment with the dopamine D2 receptor antagonist, eticlopride, blocked the increase in vesicular dopamine uptake caused by PCP administration. These data demonstrate a heretofore unreported mechanism that may contribute to the ability of PCP to influence dopamine neuronal function and exert its pharmacological effects.

Animals↗
PubMed1996

Effects of a range of dopamine receptor agonists and antagonists on ethanol intake in the rat.

The aim of this study was to assess the effects of a range of dopaminergic agents on consumption of an ethanol solution (10% ethanol, 3% glucose) in rats. A two-bottle, free-choice paradigm was used following induction of ethanol consumption and preference in standard laboratory rats. The model used provides a robust and reliable level of ethanol oral administration in normal laboratory rats. Both ethanol intake and preference were reduced by a dopamine D1 receptor partial agonist, SFK 38393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride), in a dose-dependent manner. The dopamine D2/D3 receptor agonist 7-OH-DPAT ((+/-)-7-hydroxy-N,N-(di-n-propyl-2-aminotetralin)) at the lowest dose of 0.01 mg/kg increased both ethanol intake and preference. At higher doses (0.03-0.1 mg/kg) no significant effects were found. The dopamine D1 receptor antagonist SCH 23390 (R-(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepine-8- ol), dopamine D2/D3 receptor antagonist raclopride and 5-HT2/D2 receptor antagonist risperidone did not affect ethanol consumption, although all at high doses induced a significant decrease in water intake, indicating a non-specific decrease in consummatory behavior with these compounds. These results suggest the involvement of the dopaminergic system in ethanol intake and ethanol reinforcement with dopamine D1 and D2/D3 receptors playing opposing roles. Blockade of dopamine D2 receptors had no selective effect on ethanol consumption and ethanol preference.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Preclinical evaluation of [123I]R93274 as a SPECT radiotracer for imaging 5-HT2A receptors.

Studies in rodents have suggested that the radioiodinated 5-HT2A receptor antagonist [123I]R93274 (123-iodine-N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-ami no- 5-iodo-2-methoxybenzamide) (Kd = 0.1 nM) might be a promising single photon emission computerized tomography (SPECT) radiotracer to image 5-HT2A receptors in the living human brain. In this study, we characterized the brain uptake of [123I]R93274 in baboons. Highest brain uptake was observed in cortical areas, while lower uptake was observed in the striatum and the cerebellum. Injection of pharmacological doses of the 5-HT2A receptor antagonist ketanserin resulted in reduction of cortical and striatal radioactivities to the level observed in the cerebellum. Injection of the selective dopamine D2 receptor antagonist raclopride did not affect [123I]R93274 brain uptake. Quantification of 5-HT2A receptors was achieved by measuring the binding potential of 5-HT2A receptors for [123I]R93274 (the binding potential is the product of the density and affinity of available receptors). Regional binding potential values were derived with a three-compartmental kinetic analysis of the time-activity curves in the brain and plasma. Binding potential values of 93 +/- 34 ml/g, 71 +/- 35 ml/g and 31 +/- 11 ml/g were measured in the occipital, temporal and striatal regions, respectively. Similar values were derived using a noncompartmental graphical analysis. These values were in accordance with the in vitro regional distribution of 5-HT2A receptors in primate brain. In conclusion, [123I]R93274 allows visualization and quantification of 5-HT2A receptors in the baboon brain with SPECT.

Animals↗