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J G Hensler

Publications and source records attributed to J G Hensler.

At least 19 recordsLinked to original sources
PubMed2004

Effect of valproic acid on serotonin-2A receptor signaling in C6 glioma cells.

Valproic acid (VPA), which has demonstrated efficacy in the treatment of bipolar disorder, has been shown to alter components of the phosphoinositide (PI) signaling cascade and to increase gene expression mediated by the transcription factor activator protein 1 (AP-1). Central serotonin-2A (5-HT2A) receptors, which have been implicated in the pathophysiology of manic-depressive illness, are coupled to PI hydrolysis. The promoter region of the 5-HT2A receptor gene contains AP-1 binding sites. We examined in C6 glioma cells the effect of VPA on 5-HT2A receptor signaling. Treatment of cells with VPA (100 microg/mL) for 20 h, but not 1.5 h, resulted in an enhancement of 5-HT2A receptor-stimulated PI hydrolysis. This effect of 20-h VPA exposure appeared not to be at the level of G protein or effector (i.e. phospholipase C: PLC) as inositol phosphate accumulation stimulated by aluminum fluoride or the PLC activator 2,4,6-trimethyl-N-(m-3-trifluromethylphenyl) benzenesulfonamide was not increased. The number of 5-HT2A receptors, as determined in saturation binding experiments using [3H]ketanserin, was increased by 20-h VPA treatment, with no change in affinity (KD). Taken together, our data suggest that the increase in 5-HT2A receptor-mediated PI hydrolysis following 20-h VPA exposure is not due to a general effect of VPA on this signaling cascade, but due to the up-regulation of 5-HT2A receptor number.

Animals↗
PubMed2003

Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/-) mice.

Heterozygous brain-derived neurotrophic factor (BDNF) (+/-) mice display abnormalities in central serotonergic neurotransmission, develop decrements in serotonergic innervation of the forebrain, and exhibit enhanced intermale aggressiveness. As disturbances of serotonin neurotransmission are implicated in alcohol abuse and aggression, we have examined in BDNF (+/-) mice alcohol drinking behavior, as well as central 5-hydroxytryptamine (5-HT)1A receptor function at the level of 5-HT1A receptor-G protein interaction. BDNF (+/-) mice displayed increased ethanol intake in a two-bottle choice procedure. There was no difference in the preference ratio for non-alcoholic tastants (i.e. quinine or saccharin) between genotypes. In the brains of alcohol-naive mice, we measured [35S]GTP gamma S binding stimulated by the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-dipropyl-aminotetralin hydrobromide (8-OH-DPAT; 1 microM). In BDNF (+/-) versus wild-type (WT) mice, 5-HT1A receptor-stimulated [35S]GTP gamma S binding was significantly attenuated in the median raphe nucleus. There was a decrease in (+/-)8-OH-DPAT-stimulated [35S]GTP gamma S binding in the dorsal raphe, which did not reach statistical significance. In the hippocampus, 5-HT1A receptor-stimulated [35S]GTP gamma S binding was significantly attenuated in BDNF (+/-) mice. 5-HT1A receptor-stimulated [35S]GTP gamma S binding was attenuated in the anterior cingulate cortex and lateral septum, although these reductions did not reach statistical significance. 5-HT1A receptor number was not different between genotypes in any area of brain examined, suggesting that 5-HT1A receptor function, specifically the capacity of the 5-HT1A receptor to activate G proteins, is attenuated in BDNF (+/-) mice.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2002

Selective heterologous regulation of 5-HT1A receptor-stimulated 35S GTPgammaS binding in the anterior cingulate cortex as a result of 5-HT2 receptor activation.

Previous studies have shown that administration of the 5-HT(2) receptor agonist DOI to rats results in the heterologous desensitization of 5-HT(1A) receptor-mediated behavioral and neuroendocrine responses [Neuropsychopharmacology 19 (1998) 354; J. Neurosci. 21 (2001) 7919]. We hypothesized that the basis for these changes in 5-HT(1A) receptor function may involve changes in the capacity of the 5-HT(1A) receptor to activate G proteins. We examined the effect of chronic administration of DOI on the regulation of 5-HT(1A) receptor function at the level of receptor-G protein interaction using quantitative autoradiography of [(35)S]GTPgammaS binding stimulated by the 5-HT(1A) receptor agonist (+/-)8-OH-DPAT (1 microM). Repeated administration of DOI (1 mg/kg, s.c. once daily for 8 days) resulted in a marked down-regulation in 5-HT(2A) binding sites, as labeled by the antagonist radioligand [(3)H]ketanserin, throughout the cerebral cortex. Chronic DOI treatment also resulted in a significant and selective attenuation of 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding in the anterior cingulate cortex (vehicle-treated: 74+/-7.7% above basal; DOI-treated: 43+/-4.6% above basal). Interestingly, 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding was not altered in the dorsal or median raphe, or in the limbic structures and other cortical regions examined. The decrease in 5-HT(1A) receptor-stimulated [(35)S]GTPgammaS binding in anterior cingulate cortex was not due to a decrease in 5-HT(1A) receptor number, indicating that the capacity of the 5-HT(1A) receptor to activate G proteins is attenuated in this cortical area following repeated DOI treatment. The heterologous regulation of 5-HT(1A) receptor function by chronic 5-HT(2) receptor activation in the anterior cingulate cortex raises interesting questions as to how the regulatory interaction between these serotonin receptor subtypes influences cognition, memory and emotion.

Amphetamines↗
PubMed2001

The role of protein kinase C in the regulation of serotonin-2A receptor expression.

We have investigated in C6 glioma cells the involvement of protein kinase C (PKC) in the regulation of serotonin-(2A) receptor (5-HT(2A) receptor) expression by agonist treatment. Comparison of the time-courses of agonist-induced downregulation of receptor number and mRNA indicate that a decrease in the number of 5-HT(2A) receptor binding sites in response to serotonin (5-HT) treatment is preceded by a decrease in 5-HT(2A) receptor mRNA. This decrease in 5-HT(2A) receptor mRNA as a result of agonist exposure was not due to a change in the stability or half-life of the transcript. Pretreatment of cells with the PKC inhibitor bisindolylmaleimide blocked the decrease in 5-HT(2A) receptor mRNA levels, and attenuated the down-regulation of 5-HT(2A) receptor binding sites induced by treatment with 5-HT. Experiments performed with the PKC inhibitors calphostin C and Gö 6976 confirmed that PKC was involved in the regulation of 5-HT(2A) receptor mRNA by agonist and implicate the conventional subgroup of PKC isoforms. Western blot analysis, using isoform-specific anti-PKC antibodies showed that under our culture conditions C6 glioma cells express the conventional isoforms PKC alpha, PKC gamma, as well as the novel isoforms PKC delta, PKC epsilon, and the atypical isoforms PKC lambda and PKC iota. Upon treatment with 5-HT for 10 min levels of the conventional isoforms PKC alpha and PKC gamma increased in the nuclear fraction. Taken together, our results implicate PKC alpha and/or PKC gamma in the regulation of 5-HT(2A) mRNA receptor and binding sites in response to agonist treatment.

Animals↗
PubMed2001

gamma-Aminobutyric acid (GABA)--A function and binding in the paraventricular nucleus of the hypothalamus in chronic renal-wrap hypertension.

The goal of this study was to determine whether gamma-aminobutyric acid (GABA)ergic transmission and GABA binding are altered in chronic renal-wrap hypertension. Three groups of hypertensive and sham-operated rats were prepared for separate protocols. Four weeks later, the animals were prepared with femoral artery catheters for the measurement of mean arterial pressure. In all groups, blood pressure was significantly higher in the renal-wrapped animals. In the first study, bilateral microinjection of the GABA-A antagonist, bicuculline (50 pmol/site), into the paraventricular nucleus of the hypothalamus (PVN) caused a greater increase in arterial pressure (21.9+/-1.4 versus 16.7+/-1.8 mm Hg, P<0.05) and heart rate (135+/-15 versus 98+/-12 bpm, P=0.064) in hypertensive rats. [(3)H]Flunitrazepam was used to measure binding to the GABA-A receptor. Magnocellular neurons and the adjacent medial parvicellular neurons had more intense binding compared with the remainder of the PVN. B(max) was greater for the higher density binding area; the K(d) value was less in the high-density region. There were no differences in these parameters between normotensive and hypertensive animals. Competitive reverse transcription-polymerase chain reaction was used to measure the expression of mRNA for the alpha(1) subunit of the GABA-A receptor. No difference was observed in the mRNA between renal-wrapped and sham-operated rats. In summary, inhibition of GABA-A receptors in the PVN is augmented in the chronic phase of hypertension and is unrelated to a change in the expression of the number or affinity to the receptor. These findings suggest that the greater GABAergic activity is the result of an increase in GABA release in the PVN in chronic renal-wrap hypertension.

Animals↗
PubMed2000

Regulation of 5-HT(2A) receptor mRNA levels and binding sites in rat frontal cortex by the agonist DOI and the antagonist mianserin.

In the present study we have characterized the time course of effect of administration of the serotonin(2) (5-HT(2)) receptor antagonist mianserin, or the 5-HT(2) receptor agonist (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), on 5-HT(2A) receptor binding sites and mRNA levels in rat frontal cortex. Radioligand binding and ribonuclease protection assays were performed with separate hemispheres of frontal cortex from each animal to examine concomitant changes in 5-HT(2A) receptor sites and mRNA levels. The decrease in cortical 5-HT(2A) receptor sites in response to chronic DOI administration was not accompanied by changes in 5-HT(2A) receptor mRNA. A single injection of DOI produced a transient decrease in 5-HT(2A) receptor mRNA levels detected 1 h post-injection. The density of 5-HT(2A) receptor sites, however, was not significantly reduced following a single injection of DOI. The down-regulation of cortical 5-HT(2A) receptor sites in response to a single injection of mianserin was accompanied by reductions in 5-HT(2A) receptor mRNA levels. Following 4 days of mianserin administration, however, we did not observe a change in 5-HT(2A) receptor mRNA levels, although 5-HT(2A) receptor density was decreased. Thus, changes in receptor mRNA may initially contribute to the down-regulation of 5-HT(2A) receptors in response to acute mianserin administration. Sustained changes in 5-HT(2A) receptor mRNA, however, appear not to be involved in maintaining the down-regulation of 5-HT(2A) receptor number with chronic mianserin administration. Mechanisms other than the regulation of receptor mRNA levels appear to underlie the down-regulation of 5-HT(2A) receptor sites in response to chronic administration of the agonist DOI.

Amphetamines↗
PubMed1999

Serotonin2A receptor modulation of D1 dopamine receptor-mediated grooming behavior.

We have previously observed that intracerebroventricular infusion of a 5-HT2A receptor antisense oligonucleotide for 8 days results in an increase in cortical 5-HT2A receptor sites and an increase in central 5-HT2A receptor function as measured by quantitation of 5-HT2A receptor-mediated headshake behavior (28). Because lesioning serotonergic neurons or chronic administration of 5-HT2A receptor antagonists does not result in an increase in 5-HT2A receptor density or function in the brain, we have taken advantage of this unique upregulation of 5-HT2A receptors following 5-HT2A receptor antisense oligonucleotide infusion to study the modulation of D1 receptor-mediated behaviors by 5-HT2A receptors. Grooming behavior, elicited by acute injection of SKF 38393, was attenuated after chronic ICV infusion of a 5-HT2A receptor antisense oligonucleotide. There was also a reduction in vacuous chewing behavior induced by SKF 38393, which did not reach statistical significance. Other oral behaviors (i.e., tongue protrusions and gnawing at the cage bottom) were not attenuated. An increase in the density of cortical, as well as striatal 5-HT2A receptor sites was observed following chronic antisense oligonucleotide administration. There was no change in striatal D1 dopamine receptors following 5-HT2A receptor antisense oligonucleotide administration. SKF 38393-induced grooming behavior was also attenuated in naive rats pretreated acutely with the 5-HT2 receptor agonist DOI. These results suggest a role for the 5-HT2A receptor in the modulation of D1 receptor function.

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

Effect of chronic serotonin-2 receptor agonist or antagonist administration on serotonin-1A receptor sensitivity.

We have investigated the effect of 5-HT2 receptor agonist or antagonist administration on postsynaptic 5-HT1A receptor sensitivity assessed by two behavioral measures, reciprocal forepaw treading or hypothermia induced by acute injection of the 5-HT1A receptor agonist 8-OH-DPAT. The effectiveness of these drug treatments to downregulate 5-HT2A receptors was confirmed by measuring the binding of [3H]-ketanserin in cortical homogenates, because all of these drug treatments have been shown to result in the downregulation of 5-HT2A receptor sites. Acute or chronic treatment of rats with the 5-HT2 receptor antagonist mianserin, or chronic administration of the 5-HT2A receptor antagonist ketanserin, did not alter 8-OH-DPAT-induced hypothermia or forepaw treading. These data indicate that downregulation of 5-HT2A receptors is not sufficient to alter these postsynaptic 5-HT1A receptor-mediated responses. Chronic treatment of rats with the 5-HT2 receptor agonist DOI, however, resulted in the attenuation of both 5-HT1A receptor-mediated responses measured in separate experimental groups. The apparent desensitization of 5-HT1A receptors following chronic DOI treatment was not accompanied by a change in either the number or affinity of 5-HT1A receptor sites as measured by the binding of [3H]-8-OH-DPAT in hippocampal homogenates. Chronic activation of 5-HT2 receptors may be one mechanism by which the sensitivity postsynaptic 5-HT1A receptors can be regulated.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Regulation of serotonin2A receptor expression by an antisense oligodeoxynucleotide.

The regulation of 5-HT2A receptor expression by an antisense oligodeoxynucleotide, complementary to the coding region of rat 5-HT2A receptor mRNA, was examined in a cortically derived cell line and in rat brain. Treatment of A1A1 variant cells, which express the 5-HT2A receptor coupled to the stimulation of phosphatidylinositol (PI) hydrolysis, with antisense oligodeoxynucleotide decreased the maximal stimulation of PI hydrolysis by the partial agonist quipazine and the number of 5-HT2A receptor sites as measured by the binding of 2-[125I]-iodolysergic acid diethylamide. Treatment of cells with random, sense, or mismatch oligodeoxynucleotide did not alter the stimulation of PI hydrolysis by quipazine or 5-HT2A receptor number. Intracerebroventricular infusion of antisense, but not mismatch, oligodeoxynucleotide for 8 days resulted in a significant increase in cortical 5-HT2A receptor density and an increase in headshake behavior induced by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. The density of cortical 5-HT2A receptors was not altered by administration of antisense oligodeoxynucleotide for 1, 2, or 4 days. We hypothesize that in brain this antisense oligodeoxynucleotide relieved some form of translational suppression, resulting in an increase in 5-HT2A receptor expression.

Animals↗
PubMed1996

Expression and modulation of 5-hydroxytryptamine1A receptors in P11 cells.

P11 cells were transfected with DNA for the human 5-hydroxytryptamine1A (5-HT1A) receptor. These cells stably expressed the 5-HT1A receptor coupled to the inhibition of adenylyl cyclase, and not to the stimulation of phosphoinositide hydrolysis. Homologous and heterologous regulation of the 5-HT1A receptor was studied in this cell system. Pretreatment of P11-5HT1A cells with the 5-HT1 receptor agonist 5-carbox-amidotryptamine (5-CT) resulted in a 3-fold increase in both basal and forskolin-stimulated cAMP accumulation, and desensitization of the 5-HT1A receptor as indicated by a decrease in the potency of 8-hydroxydipropylaminotetralin (8-OH-DPAT) to inhibit forskolin-stimulated cAMP accumulation (vehicle-treated cells: EC50 = 2.3 +/- 0.8 nM; 5-CT-treated cells: 9.9 +/- 0.4 nM). The sensitization of adenylyl cyclase as a result of chronic agonist exposure was prevented by the 5-HT1A antagonist WAY100635, which indicated that the effect of 5-CT pretreatment on basal and forskolin-stimulated cAMP accumulation was mediated by 5-HT1A receptor activation. Pretreatment of cells with pertussis toxin abolished the inhibition of forskolin-stimulated cAMP accumulation mediated by 5-HT1A receptor activation and prevented the sensitization of adenylyl cyclase as a result of chronic 5-HT1A receptor agonist exposure. Pretreatment of P11-5HT1A cells with the phorbol ester, phorbol 12-myristate 13-acetate (PMA), also resulted in desensitization of the 5-HT1A receptor, as indicated by a marked decrease in the potency and intrinsic activity of 8-OH-DPAT. No change in the binding characteristics (i.e., Kd or Bmax) of [3H]8-OH-DPAT to 5-HT1A receptor sites was observed after 5-CT or PMA treatments. Activation of alpha-1 adrenergic receptors, but not 5-HT2A receptors, had effects on 5-HT1A receptor responsiveness similar to those seen with PMA pretreatment. In P11-5HT1A cells, homologous regulation of the 5-HT1A receptor was characterized by sensitization of adenylyl cyclase and a decrease in agonist potency, whereas heterologous regulation of the 5-HT1A receptor was characterized by a greater decrease in agonist potency, as well as a marked decrease in intrinsic activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Quantitative autoradiography of the serotonin transporter to assess the distribution of serotonergic projections from the dorsal raphe nucleus.

The binding of 3H-CN-IMI to 5-HT uptake sites, as measured by quantitative autoradiography, was used as a marker of serotonergic neurons. Within the dorsal raphe nucleus the binding of 3H-CN-IMI was compared in adjacent coronal sections of rat brain to the binding of 3H-DPAT to 5-HT1A receptors, which have a known somatodendritic localization. The heterogeneous pattern of binding of these two radioligands within the dorsal raphe nucleus was similar and corresponded to the distribution of serotonergic cell bodies as visualized by 5-HT immunohistochemistry. Intracerebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT), which caused a dramatic loss of 5-HT immunoreactivity and 3H-DPAT binding to 5-HT1A receptors, resulted in a marked reduction of 3H-CN-IMI binding in this nucleus. Treatment of rats with a dose of para-chloroamphetamine (PCA) which has been reported to selectively lesion serotonergic processes arising from the dorsal raphe nucleus, while sparing serotonergic cell bodies and projections from the median raphe nucleus, did not alter the binding of 3H-DPAT or 3H-CN-IMI in the dorsal raphe nucleus; serotonergic cell bodies appeared morphologically unaffected. The lack of effect of PCA treatment on the binding of 3H-DPAT and 3H-CN-IMI is consistent with a somatodendritic localization of the 5-HT transporter in the dorsal raphe nucleus. PCA treatment appeared to produce a moderate loss of serotonergic innervation in serotonergic terminal field areas as visualized by serotonin immunohistochemistry. The reductions in 3H-CN-IMI binding observed in terminal field areas (24 to 69%) following treatment of rats with PCA did not reflect a marked differential innervation of forebrain areas by the dorsal and medial raphe nuclei as expected from previous biochemical studies, and were not entirely consistent with the findings of neuroanatomical studies using histochemical techniques. Site-specific injection of 5,7-DHT into the dorsal raphe nucleus produced an 80 +/- 11% reduction in the binding of 3H-CN-IMI in this nucleus, whereas the binding of 3H-CN-IMI in the median raphe nucleus was not reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1994

Characterization of [125I](R)-trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino] tetralin binding to dopamine D3 receptors in rat olfactory tubercle.

[125I](R,S)-trans-7-Hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)- amino]tetralin ([125](R,S)-trans-7-OH-PIPAT) has been shown to bind with high affinity to dopamine D3 receptors expressed in Spodoptera frugiperda cells. No specific binding was seen in Spodoptera frugiperda cells expressing a high density of D2 receptors. It was therefore, suggested that [125I] (R,S)-trans-7-OH-PIPAT selectively labels D3 receptors. In the present study, saturation binding of [125I](R)-trans-7-OH-PIPAT to membranes from rat olfactory tubercle resulted in markedly curvilinear Scatchard plots, suggesting that the radioligand was binding to more than one receptor class or affinity state. [125I] (R)-trans-7-OH-PIPAT bound with high affinity to membranes from human embryonic kidney-293 cells expressing transfected D2 or D3 receptors and to membranes from Chinese hamster ovary cells expressing serotonin1A receptors. Binding of [125I](R)-trans-7-OH-PIPAT to serotonin1A and D2 receptors was decreased or eliminated in the presence of NaCl and/or guanylyl-imidodiphosphate [Gpp(NH)p]. In the presence of Gpp(NH)p and NaCl, a linear Scatchard plot with a Kd value of 0.4 nM and a density of 100 fmol/mg of protein was obtained in membranes from rat olfactory tubercle. Agonists and antagonists inhibited binding of [125I](R)-trans-7-OH-PIPAT with a rank order of potency consistent with an interaction at D3 receptors. These results suggest that, in the presence of Gpp(NH)p and NaCl, [125I](R)-trans-7-OH-PIPAT specifically labels D3 receptors.

Animals↗
PubMed1991

Serotonergic neurons do not influence the regulation of beta adrenoceptors induced by either desipramine or isoproterenol.

It has been suggested that 5-hydroxytryptamine (serotonin)-containing neurons influence the regulation of central beta adrenoceptors caused by antidepressants. [3H]Dihydroalprenolol ( [3H] DHA) was the radioligand used in these previous studies to measure beta adrenoceptors. In this study, we compared the binding characteristics of [3H]DHA with those of [125I]iodopindolol ( [125I]PIN) and used [125I]IPIN to study effects of lesioning serotonergic nerves on the regulation of beta adrenoceptors. A comparison was made in homogenates prepared from rat frontal cortex of the specific binding of [3H]DHA with that of [125I]IPIN to beta adrenoceptors. Nonlinear regression analysis of saturation experiments of [3H]DHA binding to cortical homogenates indicated that a two-component binding model fit the data significantly better than a one-component model. A dissociation constant value of 0.47 +/- 0.16 nM and a Bmax value of 62 +/- 7 fmol/mg protein were obtained for the high-affinity site. The low-affinity site was poorly defined. Rosenthal transformations of the saturation isotherms for [3H]DHA binding were clearly curvilinear. By contrast, nonlinear regression analysis of saturation experiments of the binding of [125I]IPIN indicated that the binding of this radioligand was described adequately by a one-component model and yielded a dissociation constant value of 147 +/- 10 pM with a Bmax of 80 +/- 5 fmol/mg protein. Rosenthal transformations of the [125I]IPIN data were linear. From such data, it was inferred that [3H]DHA binds to some site in addition to beta adrenoceptors, whereas [125I]IPIN does not.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1991

A quantitative autoradiographic study of serotonin1A receptor regulation. Effect of 5,7-dihydroxytryptamine and antidepressant treatments.

There have been few studies investigating the effect of treatments that alter serotonergic neurotransmission on the density of serotonin1A (5-hydroxytryptamine1A [5-HT1A]) receptors, even though lesioning serotonergic neurons has been reported to enhance certain responses thought to be due to activation of 5-HT1A receptors and repeated treatment of rats with different types of antidepressants can diminish 5-HT1A-mediated responses. Consequently, the binding of 3H-8-hydroxy-2-(di-n-propylamino)-tetralin (DPAT) to 5-HT1A receptors in serotonergic cell body and terminal field areas of rat brain was measured by quantitative autoradiography following either the lesioning of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT), or after chronic administration of monoamine oxidase inhibitors (MAOIs) (clorgyline, phenelzine, or tranylcypromine) or inhibitors of 5-HT uptake (citalopram or sertraline). Treatment of rats with 5,7-DHT did not cause any significant increase in binding of 3H-DPAT to 5-HT1A receptors in any area of the brain examined. There was no significant reduction in the binding of 3H-DPAT in terminal field areas of serotonergic innervation in rats treated with 5,7-DHT except in the CA2/CA3 region of the hippocampus (33% to 35% reduction). In the dorsal and median raphe nuclei, the specific binding of 3H-DPAT was reduced by treatment of rats with 5,7-DHT. In lesioned rats, the binding of 3H-cyanoimipramine (3H-CN-IMI) to uptake sites for serotonin was essentially eliminated in all terminal field areas examined, as well as in the dorsal and median raphe nuclei. Repeated administration of clorgyline, phenelzine, tranylcypromine, citalopram, or sertraline produced an attenuation of the hypothermic response of rats to acute subcutaneous injection of the 5-HT1A-receptor-agonist DPAT. In spite of this change in 5-HT1A responsivity, these treatments caused in the same animals no consistent change in the binding of 3H-DPAT in either serotonergic cell body or terminal field areas. Of the five drugs studied that diminished DPAT-induced hypothermia, only phenelzine and clorgyline significantly reduced the binding of 3H-DPAT, and even then in only a few of the 12 areas of brain measured. As a result of treatment of rats with tranylcypromine there was a significant increase in the binding of 3H-DPAT in the CA2/CA3 region of the hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1988

GABAergic modulation of D-1 dopamine receptor-mediated 3H-acetylcholine release from rabbit retina.

Dopamine evokes calcium-dependent release of 3H-acetylcholine from superfused rabbit retina labeled in vitro with 3H-choline, through activation of a D-1 dopamine receptor. This study investigates the activation of this receptor by endogenous dopamine and the modulation of the spontaneous and dopamine-evoked release of 3H-acetylcholine from rabbit retina labeled with 3H-choline by GABAergic agonists and antagonists. Endogenous dopamine, released from dopaminergic amacrine neurons by the indirect amines tyramine or D-amphetamine evoked the calcium-dependent release of 3H-acetylcholine from rabbit retina. The release of 3H-acetylcholine elicited by tyramine (10 microM) or D-amphetamine (10 microM) was attenuated by the selective D-1 antagonist SCH 23390 (0.1 microM) and by the dopamine uptake inhibitor nomifensine (3 microM). At concentrations of 1 mM and 1 microM respectively, GABA and muscimol inhibited the spontaneous release of tritium from rabbit retina labeled in vitro with 3H-choline. Picrotoxin and bicuculline (10 microM) increased the spontaneous release of tritium. GABA and the GABA agonist muscimol (0.01-100 microM) inhibited in a concentration-dependent manner the release of 3H-acetylcholine elicited by 100 microM dopamine with IC50 values of 4.5 microM and 0.02 microM respectively. The inhibition of dopamine-evoked 3H-acetylcholine release by GABA (10 microM) and muscimol (0.1 microM) was antagonized by the GABA antagonists bicuculline and picrotoxin. Picrotoxin and bicuculline (10 microM) increased the spontaneous release of tritium, and potentiated the release of 3H-acetylcholine evoked by 100 microM dopamine consistent with a tonic, inhibitory GABAergic input to the cholinergic amacrine neurons in rabbit retina.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗