This study was conducted to determine whether photoperiod-induced changes in serum concentrations of prolactin in cattle were associated with changes in activity of dopamine or 5-hydroxytryptamine (5-HT) neurones in the infundibulum/pituitary stalk and the secretion rate and number of lactotrophs in the anterior pituitary gland. Sixteen prepubertal bull calves (approximately 8 weeks of age) were divided into two groups. One group of eight was maintained on a photoperiod of 8 h light: 16 h darkness (8L:16D) and the other group was exposed to 16L:8D for 4 weeks. At this time calves were injected with a decarboxylase inhibitor (m-hydroxybenzylhydrazine dihydrochloride, NSD 1015) which blocks the conversion of dihydroxyphenylalanine (DOPA) to dopamine and of 5-hydroxytryptophan (5-HTP) to 5-HT. Calves were killed with pentobarbital 15 min later. Accumulations of DOPA and 5-HTP in selected brain regions were used as indices of activity of dopamine and 5-HT neurones respectively. Secretory rate and number of prolactin-secreting lactotrophs were determined by reverse haemolytic plaque assay. Relative to calves exposed to 8L:16D, exposure to 16L:8D increased serum concentrations of prolactin by eightfold, anterior pituitary gland weight by 23%, release of prolactin from pituitary explants by 57% and the area of the plaque for prolactin-secreting lactotrophs by 70%. There was no difference in the rates of accumulation of DOPA and 5-HTP in the infundibulum/pituitary stalk of animals exposed to 4 weeks of 16L:8D or 8L:16D.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of elevated circulating concentrations of prolactin were examined on neurochemical estimates of activity of dopaminergic neurons in the infundibulum/pituitary stalk of Holstein bull calves (8-10 weeks of age). Activity of these neurons was estimated by measuring the accumulation of dihydroxyphenylalanine, the immediate precursor of dopamine, 15 min after an intravenous injection of the aromatic L-amino acid decarboxylase inhibitor, 3-hydroxybenzylhydrazine. Subcutaneous injections of the dopamine antagonist haloperidol every 6 hr for 1 day increased serum concentrations of prolactin and accumulation of dihydroxyphenylalanine in the infundibulum/stalk. Intravenous infusions of prolactin for 1 or 9 days increased accumulation of dihydroxyphenylalanine in the infundibulum/stalk, indicating that these neurons remain responsive to elevated prolactin for at least 9 days. It is concluded that elevated concentrations of prolactin in blood stimulate dopaminergic neurons in the infundibulum/pituitary stalk of bull calves. We speculate that these neurons may be analogous to the tuberoinfundibular dopaminergic neurons that regulate prolactin in rats.

Concentrations of dopamine (DA) and one of its major metabolites, dihydroxyphenylacetic acid (DOPAC), were determined in selected brain regions of rats that were euthanatized either by decapitation or by intravenous injections of pentobarbital or Fatal Plus, a commercial preparation that contains pentobarbital. When compared with values in decapitated brains, pentobarbital increased the concentration of DOPAC in the median eminence, which contains terminals of tuberoinfundibular dopaminergic (TIDA) neurons. Fifteen minutes of restraint reduced the concentration of DOPAC in the median eminence of rats killed by decapitation or by injections of pentobarbital, indicating that pentobarbital does not mask restraint-induced decrease in TIDA neuronal activity. In contrast, none of the manipulations altered DA or DOPAC concentrations in the striatum, which contains terminals of nigrostriatal dopaminergic neurons. Thus, changes in the concentrations of DOPAC in the median eminence (an index of TIDA neuronal activity) induced by stress can be detected in rats euthanatized by either decapitation or an injection of pentobarbital.

Administration of gamma-butyrolactone (GBL), an anesthetic which reduces dopaminergic neuronal activity, decreased the concentration of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the intermediate lobe of the pituitary gland, and increased alpha-melanocyte stimulating hormone (alpha MSH) concentrations in the serum of male rats. Bilateral electrical stimulation of the rostral arcuate nucleus, which contains perikarya of tuberohypophysial DA neurons, increased DOPAC concentrations in the intermediate lobe and decreased alpha MSH concentrations in the serum of GBL-anesthetized rats. Administration of the DA antagonist haloperidol prevented the decline in serum alpha MSH levels following arcuate nucleus stimulation, but had no effect on serum alpha MSH concentrations in sham-stimulated GBL-treated rats. These results indicate that GBL-induced decreases or stimulation-induced increases in the activity of tuberohypophysial DA neurons are accompanied by corresponding changes in the metabolism of DA in the intermediate lobe of the rat pituitary gland, and by reciprocal changes in the secretion of alpha MSH.

Perikarya and terminals of tuberoinfundibular dopaminergic (TIDA) neurons are located in the arcuate nucleus (ARN) and in the median eminence (ME), respectively. Dopamine (DA) released from TIDA terminals in the ME inhibits prolactin secretion from the anterior pituitary. Anatomical studies have described the sources of afferents to ARN and ME, but not to TIDA neurons per se. The ventromedial nucleus (VMN) and the dorsomedial nucleus (DMN) of the hypothalamus project to ARN and ME and have a role in prolactin regulation. In the present study, VMN and DMN were investigated as possible sources of TIDA afferents. Alterations in the activity of TIDA neurons were estimated by measuring plasma concentrations of prolactin and the rates of DA synthesis (3,4-dihydroxyphenylalanine - DOPA - accumulation after administration of the decarboxylase inhibitor NSD 1015) and metabolism (concentrations of the DA metabolite 3,4-dihydroxyphenylacetic acid - DOPAC) in the ME following electrical stimulation of ARN, VMN, and DMN in ovariectomized female rats. Thirty minutes of bilateral stimulation of ARN or DMN increased DOPA accumulation in the ME; stimulation of the VMN had no effect. 5-Hydroxytryptamine synthesis in the ME was unaffected by stimulation of any region. Plasma prolactin levels declined during DMN stimulation, varying with the frequency and duration of the electrical stimulus. DA metabolism within TIDA neurons increased with DMN stimulation, as evidenced by increased DOPAC concentrations in the ME. In females whose basal TIDA activity has been increased by haloperidol treatment or decreased by bromocriptine treatment, DMN stimulation was still able to increase DOPA accumulation in the ME. The present data suggest the presence of stimulatory TIDA afferents originating from or passing through the DMN.

Annals of the New York Academy of SciencesVolume 473, Issue 1 p. 303-320 Drug-Induced Changes in the Efflux of Dopamine and Serotonin Metabolites from the Brains of Freely Moving Ratsa KENNETH E. MOORE, KENNETH E. MOORE Department of Pharmacology and Toxicology Michigan State University East Lansing, Michigan 48824Search for more papers by this author KENNETH E. MOORE, KENNETH E. MOORE Department of Pharmacology and Toxicology Michigan State University East Lansing, Michigan 48824Search for more papers by this author First published: December 1986 https://doi.org/10.1111/j.1749-6632.1986.tb23625.xCitations: 6 a Supported by U.S. Public Health Service grant NS15911. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Carmichael, E. A., W. Feldberg & K. Fleischauer. 1964. Methods for perfusing different parts of the cat's cerebral ventricles with drugs. J. Physiol. (London) 173: 354–367. 2 Ashkenazi, R., R. B. Holman & M. Vogt. 1972. Release of transmitters on stimulation of the nucleus linearis raphe in the cat. J. Physiol. (London) 223: 255–259. 3 Bhattacharya, B. K. & W. Feldberg. 1958. 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Inhibition by clonidine in vivo. J. Pharmacol. Exp. Ther. 221: 541–546. Citing Literature Volume473, Issue1Neurochemical Analysis of the Conscious Brain: Voltammetry and Push‐Pull PerfusionDecember 1986Pages 303-320 ReferencesRelatedInformation

Studies were undertaken to characterize the relationship between anterior pituitary dopamine (DA) content and changes in PRL secretion that occur during physiological states in which changes in tuberoinfundibular DA neuronal activity have been previously characterized. The results of these studies are summarized as follows. Serum PRL concentrations and the anterior pituitary DA content were not different between male and diestrous female rats, an unexpected result considering that tuberoinfundibular DA neuronal activity in female rats is 2- to 3-fold greater than that in male rats. The surge of PRL secretion during the afternoon of proestrus was accompanied by a significant decrease in the anterior pituitary content of DA. Increases in PRL secretion that occur early in pregnancy and during suckling were accompanied by a decrease in tuberoinfundibular DA neuronal activity and a decrease in the DA content in the anterior pituitary. Restraint stress increased PRL secretion and reduced the anterior pituitary DA content in both male and female rats, although only female rats respond to immobilization with a decrease in tuberoinfundibular DA neuronal activity. In both male and female aged rats, there were increases in serum PRL concentrations and the anterior pituitary DA content, despite the fact that tuberoinfundibular DA neuronal activity is reduced in the aged rat. Dehydration induced by water deprivation was associated with a small increase in serum PRL concentrations and a large increase in anterior pituitary DA content; similar water deprivation regimens have induced no change in indices of tuberoinfundibular DA neuronal activity. These results demonstrate that there is not a simple relationship among physiologically induced changes in PRL secretion, anterior pituitary DA content, and tuberoinfundibular DA neuronal activity. The results also indicate that the content of DA in the anterior pituitary cannot be used as a reliable index of tuberoinfundibular DA neuronal activity.

Journal Article Effect of systemic and intrastriatal injections of haloperidol on striatal dopamine and DOPAC concentrations in rats pretreated by section of nigrostriatal fibres Get access S M Wuerthele, S M Wuerthele Department of Pharmacology and Toxicology Michigan State University, East Lansing, Michigan 48824, USA Search for other works by this author on: Oxford Academic Google Scholar K E Moore K E Moore Department of Pharmacology and Toxicology Michigan State University, East Lansing, Michigan 48824, USA Correspondence: Department of Pharmacology and Toxicology Michigan State University, East Lansing, Michigan 48824, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 32, Issue 1, September 1980, Pages 507–510, https://doi.org/10.1111/j.2042-7158.1980.tb12981.x Published: 12 April 2011 Article history Received: 05 November 1979 Published: 12 April 2011

Co-localization of the expression of the dopamine transporter (DAT) with the catecholamine synthesising enzyme tyrosine hydroxylase (TH) has been investigated using transgenic mice expressing Cre recombinase (Cre) dependent green fluorescent protein (GFP) under the control of the DAT promoter (DATIREScre/GFP). Brain sections from adult female mice were stained for Cre-induced GFP and TH using immunohistochemistry, revealing a high degree of co-expression in the midbrain dopaminergic neurons (A8-10) with the exception of the periaqueductal and dorsal raphe nuclei where dual-labelling was notably lower. In contrast, most of the rostral groups of TH-expressing neurons in the forebrain (A11, A13 − A15) showed little or no co-localization with Cre-induced GFP. Interestingly, a subpopulation of about 30% of the TH-immunoreactive neurons in the arcuate nucleus (A12) also express GFP staining. This observation supports the proposal that this hypothalamic cluster of dopaminergic neurons is neurochemically, and thus potentially functionally, heterogeneous. This study extends earlier literature focusing primarily on DAT expression in midbrain structures to demonstrate a heterogeneity of DAT and TH co-localization in forebrain neurons, particularly those in the hypothalamus. It also highlights the importance of carefully selecting and validating transgenic mouse lines when studying dopaminergic neurons.

Acute injections of baclofen or gamma-butyrolactone (GBL) into mice caused dose-dependent depression of locomotor activity and an elevation of the dopamine content and a reduction of dopamine turnover in the brain. An acute injection of baclofen, but not of GBL, was less effective in producing these effects in mice maintained on a diet containing baclofen for 10 to 12 days. This suggests that baclofen and GBL may influence dopamine neurons by different mechanisms. Acute injections of both baclofen and GBL were less effective in producing behavioral and neurochemical effects in mice pre-treated for 13 days with injections of GBL. Tolerance to the behavioral and neurochemical actions of baclofen and GBL do not appear to be the result of metabolic tolerance but possibly result from changes in the properties of the dopamine neurons.

A sensitive radioenzymatic procedure was used to quantify the effect of haloperidol on dopamine concentrations and rates of turnover in rat striatum, olfactory tubercle and median eminence, regions containing terminals of nigrostriatal, mesolimbic and tuberoinfundibular neurons, respectively. Haloperidol (2.5 mg/kg s.c.) did not alter the steady-state concentrations of dopamine in any of these brain regions at any time. Haloperidol increased dopamine turnover in the striatum and olfactory tubercle 2 and 8 hours after adminstration. The rate of dopamine turnover was increased only in the median eminence 16 and 24 hours after the administration of haloperidol, and effect which was blocked by hypophysectomy. Two other antipsychotic agents, clozapine and thioridazine, also increased dopamine turnover in the median eminence 16 hours after the first of two injections. These results provide evidence for the existence of hormonal neuronal feedback modulation of tuberoinfundibular dopaminergic neurons in contrast to the neuronal feedback modulation of nigrostriatal and mesolimbic neurons.

After labeling the caudate nucleus of spinal-sectioned cats with 3H-dopamine and perfusing the cerebroventricular system, d - or l -amphetamine, amantadine or tyramine was added to the perfusion inflow. All four drugs caused a concentration-related efflux of 3H-dopamine into the ventricular effluent. When the experiment was repeated using cats with chronic lesions of the nigro-striatal dopaminergic fibers, the drug-evoked efflux was greatly reduced. When similar lesions were made during perfusate collection. a significant drop in 3H-dopamine efflux occurred. The ability of amphetamine and amantadine to increase 3H-dopamine efflux was markedly decreased by this acute lesion; the efflux indueed by tyramine was unaffected. Low concentrations of amphetamine or amantadine but not tyramine, potentiated the efflux of 3H-dopamine elicited by low frequency nigro-striatal pathway stimulation. Thus, the efflux of 3H-dopamine evoked from central dopaminergic synapses by amphetamine and amantadine is primarily dependent upon the impulse activity of neurons in the nigro-striatal pathway; the release by tyramine, although arising from the same terminals, is not dependent upon ongoing impulse activity.

Abstract The extent of synthesis of [14C]noradrenaline from [14C]tyrosine and from [14C]dopamine was assessed in slices of superior cervical ganglia, representing cell bodies, and in submaxillary salivary glands, representing terminals of noradrenergic neurons of the cat. Immediately and 6 h after preganglionic stimulation for 3 h the rate of synthesis of noradrenaline from tyrosine and dopamine was not altered in ganglia. In salivary glands, however, synthesis of noradrenaline from both tyrosine and dopamine was increased at both times. These results suggest that acute periods of increased neural activity results in the acceleration of noradrenaline synthesis in the terminals but not in the cell bodies of noradrenergic neurons.

After dopamine stores in the caudate nucleus of cats were labeled with [(3)H]dopamine, the ventricular system was perfused with artificial cerebrospinal fluid. The addition of amantadine to the perfusing fluid caused a doserelated increase in the concentrations of [(3)H]dopamine appearing in the perfusion effluent. Subthreshold concentrations of amantadine also enhanced the efflux of [(3)H]dopamine induced by electrical stimulation of the caudate nucleus.

One hr after the injection of dl-3H-norepinephrine into various regions of the cat cerebroventricular system, the ventricles were perfused with an artificial cerebrospinal fluid (CSF). This perfusing fluid was pumped into the left lateral ventricle at a rate of 0.1 ml/min and collected at 10-min intervals from a catheter in the cerebral aqueduct or in the cisterna magna. Two hr after the perfusion was initiated the amount of radioactivity in the effluent remained relatively steady. At this time the ventricular system was perfused for 30 min with CSF containing various concentrations of d- or l-amphetamine. d-Amphetamine sulfate (25–400 μg/ml) caused an immediate increase in the content of 3H-norepinephrine in the effluent; after a latent period of 10–20 min there was also a significant increase in the effluent content of 3H-normetanephrine while the concentration of deaminated-O-methyl metabolites did not change. l-Amphetamine sulfate (50 μg/ml) did not significantly increase the amount of 3H-norepinephrine or 3-Hnormetanephrine in the perfusion effluent. d-Amphetamine caused a greater increase in the effluent concentration of 3H-norepinephrine and 3H-normetanephrine when the amine was injected into the lateral ventricle than when it was injected into the third ventricle or cisterna magna. Intravenous injections of d-amphetamine (1 mg/kg) also increased the content of 3H-norepinephrine in the perfusion effluent. After injections of 3H-dopamine into the lateral ventricle, d-amphetamine increased the efflux of both 3H-norepinephrine and 3H-dopamine, whereas after the intraventricular administration of 14C-inulin or 14C-urea, the effluent content of these inert substances was not increased by d-amphetamine. These results indicate that amphetamine increases the efflux of catecholamines from structures bordering the cerebroventricular system by blocking the reuptake process, or enhancing the release mechanism, or both.

Rats were prepared and maintained with high cervical transections in order to study learning in an intact brain that is isolated from uncontrolled sensory input and immobilized, allowing ready access to central physiological mechanisms. Stimulation electrodes were aimed at loci associated with response reinforcing processes. A response sensor was placed in the mouth to record both learned and evoked biting. All experimental subjects were trained successfully to discriminate the presence of an exteroceptive stimulus that indicated availability of the brain stimulation for biting. An intact control subject performed similarly in a lever pressing situation for brain stimulation. Biting also was evoked in both experimental and control subjects following removal of reinforcers, in a relation like that previously demonstrated between withdrawal of reinforcers and attack. The value of the experimental procedure in the study of the neural bases of learning and of the interactions between learned and inherent response processes is discussed.

Journal Article Behavioural effects of α-methyltyrosine administered in the diets of mice pretreated with a monoamine oxidase inhibitor Get access Kenneth E Moore Kenneth E Moore Department of Pharmacology, Michigan State University, East Lansing, Michigan 48823, U.S.A Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 20, Issue 8, August 1968, Pages 656–657, https://doi.org/10.1111/j.2042-7158.1968.tb09831.x Published: 12 April 2011 Article history Received: 07 June 1968 Published: 12 April 2011