The noradrenergic cyclic AMP generating system in the limbic forebrain: Pharmacological characterization in vitro and possible role of limbic noradrenergic mechanisms in the mode of action of antipsychotics

Blumberg, Jeffrey B.; Vetulani, Jerzy; Stawarz, Robert J.; Sulser, Fridolin

doi:10.1016/0014-2999(76)90043-1

Cited by 103 publications

(8 citation statements)

References 17 publications

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“…Twenty-four hours after the last desipramine injection, the animals were decapitated and the cyclic AMP responses to isoproterenol were determined. The 39.7 ± 6.2* (10) Lesion; saline 50.0 ± 2.5 (11) 62.7 ± 8.9 (12) Lesion; desipramine 50.1 ± 5.0 (11) 30.0 ± 5.1t (10) *Significantly different from corresponding value for nonlesioned animals given saline (P < .001). tSignificantly different from corresponding value for lesioned animals given DHT (P < .005).…”

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confidence: 93%

“…One-half of the frontal cortex was immediately used for studies of the cyclic AMP response to NE or isoproterenol, and the other half was frozen and used for studies of 0-adrenergic receptor binding and for analysis of serotonin and NE. The sensitivity of the cyclic AMP-generating system to NE and isoproterenol was determined in cortical slices (11,12). Cyclic AMP was isolated by ion-exchange chromatography and assayed by the protein binding method of Gilman (13).…”

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confidence: 99%

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Role of Serotonergic Input in the Regulation of the β-Adrenergic Receptor-Coupled Adenylate Cyclase System

Janowsky

Okada

Manier

et al. 1982

Science

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174

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The action of desipramine on the norepinephrine-sensitive adenylate cyclase system and the density of beta-adrenergic receptors in rat cortex was studied after selective lesioning of serotonergic neurons with 5,7-dihydroxytryptamine. In animals with lesions desipramine failed to reduce the density of beta-adrenoceptors but decreased the response of adenosine 3',5'-monophosphate to isoproterenol and norepinephrine to the same degree as in animals without lesions. The results demonstrate a functional linkage between serotonergic and noradrenergic systems in the rat cortex, with beta-adrenergic receptors and neurohormonal sensitivity of the adenosine 3',5'-monophosphate-generating system being under separate regulatory control.

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confidence: 93%

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confidence: 99%

Role of Serotonergic Input in the Regulation of the β-Adrenergic Receptor-Coupled Adenylate Cyclase System

Janowsky

Okada

Manier

et al. 1982

Science

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174

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“…CLOZ also antagonizes the effect of NE on Purkinje cells in the cerebellum (Marwah et al, 1981). The lethality produced by NE administration (Niemegeers and Janssen, 1979), and the NE-induced increase in limbic forebrain levels of CAMP, are antagonized by CLOZ (Blumberg et al, 1976;Sulser and Robinson, 1978). CLOZ-induced hypothermia and ataxia in mice are antagonized by various lipophilic a1 agonists (Menon et al, 1988(Menon et al, , 1990.…”

Section: Functional Studiesmentioning

confidence: 94%

Pharmacological actions of the atypical antipsychotic drug clozapine: A review

Ashby

Wang

1996

Synapse

164

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Clozapine [8-chloro- 11-(4-methyl- 1-piperazinyl)-3H-dibenzo (b,e)(1,4) diazepine], or clozaril, is a member of the dibenazepine class of antipsychotic drugs. Initially, studies in animals using a number of neurochemical, biochemical, electrophysiological, and behavioral paradigms indicated that clozapine was markedly different from various typical antipsychotic drugs such as haloperidol and chlorpromazine. Subsequently, clinical studies have shown that clozapine is effective in ameliorating the core symptoms, as well as the negative symptoms, in schizophrenia. However, clozapine has a much lower propensity for inducing neurological side effects after acute or repeated administration compared to various typical neuroleptics. Furthermore, clozapine is therapeutically effective in treating about 30% of schizophrenic patients who are resistant to standard antipsychotic drugs. Based on the above information, clozapine has been designated an atypical antipsychotic drug. However, at this time, it is not entirely clear why clozapine is such a unique antipsychotic drug. To date, there has not been a comprehensive review regarding clozapine's pharmacological profile. Therefore, we will review clozapine's profile in the following areas: 1) affinity for neurotransmitter receptors in the brain; 2) electrophysiology (in vivo, single-cell recording and iontophoresis; in vitro studies); 3) in vivo microdialysis and voltammetry; 4) monoamine turnover or metabolism; 5) intermediate early gene expression; 6) positron emission tomography studies; and 7) molecular biological studies. We will also compare and contrast clozapine's acute and chronic effects, and discuss the merits of various hypotheses that have been put forward to explain clozapine's unique profile.

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“…Animals at each stage of the estrous cycle were killed by decapitation during the morning. Brains were quickly removed and the striatum and the limbic forebrain dissected (Glowinsky and Iversen, 1966;Blumberg et al, 1976). Tissues were immediately frozen at -70 ~ until assay.…”

Section: Animalsmentioning

confidence: 99%

Nigrostriatal and mesolimbic dopaminergic activities were modified throughout the ovarian cycle of female rats

Fernández‐Ruiz

Hernández

Miguel

et al. 1991

J. Neural Transmission

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In this work, we have studied the changes in the functional state of nigrostriatal (NSDA) and mesolimbic (MLDA) dopaminergic neurons during the estrous cycle of the female rat. The activity of tyrosine hydroxylase (TH), the turnover rate (Kt) after inhibition of dopamine (DA) synthesis and the ratio between the contents of this amine and its metabolite, L-3,4 dihydroxyphenylacetic acid (DOPAC), were used as indices of neuronal activity. The neuronal activity of NSDA neurons rose during estrous and declined during proestrous, as reflected by the values of Kt and DOPAC/DA ratio measured during both phases. Interestingly, the course of variations in striatal TH activity was similar, although retarded in relation to the changes in neuronal activity. Thus, TH activity was high during diestrous, whereas it was low during estrous. The activity of MLDA neurons was reduced during proestrous. This can be concluded from the decreased Kt and DOPAC/DA ratio measured in this phase and it was accompanied by a low TH activity. Thereupon, both Kt and TH activity increased during estrous. These results indicate the existence of physiological changes in the functional state of both dopaminergic systems during the ovarian cycle, which are partially different for each neuronal pathway. This supports the existence of a specific regulation, and not indiscriminate effects, by the hormones involved in this cycle, mainly estradiol and progesterone.

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The noradrenergic cyclic AMP generating system in the limbic forebrain: Pharmacological characterization in vitro and possible role of limbic noradrenergic mechanisms in the mode of action of antipsychotics

Cited by 103 publications

References 17 publications

Role of Serotonergic Input in the Regulation of the β-Adrenergic Receptor-Coupled Adenylate Cyclase System

Role of Serotonergic Input in the Regulation of the β-Adrenergic Receptor-Coupled Adenylate Cyclase System

Pharmacological actions of the atypical antipsychotic drug clozapine: A review

Nigrostriatal and mesolimbic dopaminergic activities were modified throughout the ovarian cycle of female rats

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