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Biomedical subjects

G A Gerhardt

Publications and source records attributed to G A Gerhardt.

At least 91 records · Page 5Linked to original sources
PubMed1994

A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: II. Correlations with psychopathology.

As part of a multidimensional study of cerebrospinal fluid biogenic amine metabolites in schizophrenia, the relationship between neurochemical measures and psychopathology assessed using the Psychiatric Symptom Assessment Scale (PSAS) was analyzed. In a group of 20 unmedicated patients, 3,4-dihydroxyphenylacetic acid (DOPAC) was a predictor of symptom severity in a stepwise multiple regression model. Values of 3-hydroxykynurenine and metanephrine in the unmedicated state predicted clinical response in a stepwise multiple regression model, as measured by improvement in PSAS mean item score following 6 weeks on a standard dose of neuroleptic. In a subgroup of 14 patients in whom both off- and on-medication concentrations of cerebrospinal fluid biogenic amines and metabolites were measured, change in 3-hydroxykynurenine predicted clinical outcome in a multiple regression model. These findings point toward the need to examine the role of the kynurenine pathway of tryptophan metabolism in the pathophysiology of schizophrenia.

Adult↗
PubMed1994

NGF and anti-transferrin receptor antibody conjugate: short and long-term effects on survival of cholinergic neurons in intraocular septal transplants.

We describe a new molecular carrier system that allows for the transport of nerve growth factor (NGF) across the blood-brain barrier (BBB), as assessed by trophic effects on intraocular forebrain transplants that contain central cholinergic neurons. The carrier system involves monoclonal antibodies (OX-26) directed against the transferrin receptor, to which NGF molecules are covalently linked. Transferrin receptors are highly concentrated on brain blood vessels and participate in the transport of iron across the BBB. Host rats with septal transplants were divided into four groups, which received OX-26-NGF, OX-26, NGF or saline intravenously at 2, 4, 6 and 8 weeks after grafting. Half of the animals were killed directly after the final injection, whereas the other half were allowed to survive for an additional 5 months. Control experiments revealed that blood vessels in mature brain grafts in oculo contained large amounts of transferrin receptors. Covalent binding of NGF to the OX-26 antibodies did not impede OX-26 binding to CNS transferrin receptors, nor did conjugation affect the bioactivity of NGF. A time-dependent increase in host brain NGF levels was found after injection of OX-26-NGF into the tail vein. Host serum contained some NGF antibodies in the short-term OX-26-NGF group that had disappeared in the long-term group; host adrenals showed no differences in wet weight or norepinephrine or epinephrine whole tissue levels in any of the groups. As previously reported, the overall growth of intraocular septal transplants was approximately twice as great in the OX-26-NGF group relative to all other groups. This difference in final size persisted unabated for at least 5 months after the last injection. Furthermore, the significantly higher numbers of choline acetyl transferase immunoreactive neurons in transplants of OX-26-NGF-treated hosts also persisted during the 5-month postinjection interval. Taken together, the data suggest that the OX-26 conjugate may be a unique approach to permit passage of neurotrophin peptides into the brain in a biologically active form.

Adrenal Glands↗
PubMed1993

Ethanol inhibits the uptake of exogenous norepinephrine from the extracellular space of the rat cerebellum.

Rapid chronoamperometric recordings using nafion-coated carbon fiber electrodes coupled with pressure-ejection of drugs were used to investigate the effects of ethanol on norepinephrine (NE)-containing nerve terminals in the urethane-anesthetized Fischer 344 rat. Local application of ethanol from a double-barrel micropipette did not produce detectable changes in extracellular levels of NE in the rat cerebellar cortex. However, when ethanol was applied prior to local application of NE, it was seen to inhibit the uptake of NE from the extracellular space. These results were compared to the effects seen from the local application of a known high-affinity uptake inhibitor, nomifensine. Nomifensine was found to inhibit the extracellular uptake of NE in rat cerebeller cortex similar to ethanol. Our results support the hypothesis that one effect of ethanol on the noradrenergic system of the rat cerebellum is an alteration in the uptake of NE into NE-containing nerve endings. In addition, the present data concerning ethanol-induced inhibition of NE clearance or uptake support our previous electrophysiological studies in which we found that ethanol can potentiate the modulatory effects of beta-agonists on GABA responses of cerebellar Purkinje neurons.

Animals↗
PubMed1993

Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats.

In the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease, controversy exists concerning the use of apomorphine- or D-amphetamine-induced rotations as reliable indicators of nigrostriatal dopamine depletion. Our objective was to evaluate which, if either, drug-induced behavior is more predictive of the extent of nigrostriatal dopamine depletion. Fischer 344 and Sprague-Dawley rats were unilaterally injected with 9 micrograms/4 microliters/4 min 6-hydroxydopamine into the medial forebrain bundle. The animals were behaviorally tested with apomorphine (0.05 mg/kg, s.c.) and D-amphetamine (5.0 mg/kg, s.c.). Following testing, the brains were removed and the right and left striata, substantia nigra and ventral tegmental area were dissected free and quickly frozen at -70 degrees C for analysis of catecholamine content by high performance liquid chromatography coupled with electrochemical detection. Our results indicate that an animal which has greater than a 90% depletion of dopamine in the striatum might not rotate substantially on apomorphine, without a concomitant depletion of > 50% of the DA content in the corresponding substantia nigra. No correlations were seen involving depletions of the ventral tegmental area and the extent of the lesions to the striatum. Submaximally lesioned (75-90% depleted) rats were found to rotate on D-amphetamine but not on apomorphine. In addition, control rats that did not receive lesions were often seen to rotate extensively on D-amphetamine. We therefore conclude that maximal lesions of the striatum and substantia nigra are required to generate rotations demonstrable with low dose apomorphine but not with D-amphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1993

In vivo electrochemical measurements of exogenous dopamine clearance in normal and neonatal 6-hydroxydopamine-treated rat striatum.

The regulation of extracellular dopamine (DA) levels was studied in rat striatum after neonatal dopamine lesions and enhanced serotonin (5-HT) fiber ingrowth, induced with 6-hydroxydopamine (6-OHDA). We used rapid in vivo chronoamperometry combined with local DA applications. DA was pressure ejected in doses of 5 to 100 pmol at a distance of approximately 300 microns from the recording electrode, using single- or multibarrel glass micropipettes. Almost twice as much DA had to be applied in control rat dorsal and ventral striatum to obtain signals comparable to those recorded in the neonatal 6-OHDA-treated animals. In addition, in the dorsal striatum, the later portions of the DA clearance signals were significantly prolonged in the 6-OHDA group. Some clearance decay times in ventral striatum were also significantly prolonged in the neonatal 6-OHDA-treated rats. Concomitant application of the DA uptake inhibitor, nomifensine, in conjunction with the DA ejections, produced signal characteristics in the control striatum that were similar to those seen in the neonatal 6-OHDA-treated striatum. Taken together, these data support the hypothesis that a major component of the clearance of extracellular DA is dependent on intact terminals with high-affinity DA uptake, and that loss of DA afferents from neonatal 6-OHDA treatment results in a slowed clearance time of extracellular DA which is not apparently compensated by the enhanced 5-HT fiber ingrowth.

Animals↗
PubMed1993

In vivo electrochemical measurements and electrophysiological studies of rat striatum following neonatal 6-hydroxydopamine treatment.

The effects of neonatal treatment (one day after birth) with the neurotoxin, 6-hydroxydopamine (75 micrograms/10 microliters intracisternal), were studied in the striatum of normal adult and treated Sprague-Dawley rats. Measurements of monoamine levels in the dorsal striatum and nucleus accumbens, by high-performance liquid chromatography coupled with electrochemical detection, showed that neonatal 6-hydroxydopamine treatment produced a permanent and massive destruction of striatal dopamine. The effects were more pronounced in the dorsal striatum than in the nucleus accumbens. In addition, serotonin levels were elevated in the rat striatum as a consequence of the neonatal treatment. Rapid chronoamperometric recordings of K(+)-evoked monoamine overflow using Nafion-coated recording electrodes were investigated in both the dorsal and ventral striatum of control and neonatally lesioned rats. The potassium-evoked responses recorded from the dorsal striatum of the 6-hydroxydopamine-treated rats were significantly reduced in amplitude as compared to controls. In addition, the reduction/oxidation current ratios of the responses were more serotonin-like, in contrast to the dopamine-like current ratios measured in the striatum of untreated animals. In ventral striatum, the amplitudes of the K(+)-evoked responses were not significantly reduced versus control. However, the K(+)-evoked signals were more serotonin-like in their electrochemical characteristics as compared to controls. In addition to the release studies, extracellular single-unit electrophysiological recordings were performed in normal and neonatally 6-hydroxydopamine-treated rats. The spontaneous discharge rate of striatal neurons in the neonatally 6-hydroxydopamine-treated rats was similar to that of control rats. This is in contrast to dopamine lesions in adult animals, where a marked elevation of the discharge rate is observed. Local applications of dopamine and serotonin into the striatum of neonatally 6-hydroxydopamine-treated rats elicited excitations of striatal cells rather than the normal inhibitory effects seen in control animals. Taken together, these data suggest that loss of striatal dopamine terminals at birth leads to both pre- and postsynaptic alterations in monoamine pathways.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Reduced clearance of exogenous dopamine in rat nucleus accumbens, but not in dorsal striatum, following cocaine challenge in rats withdrawn from repeated cocaine administration.

We investigated whether changes in the dopamine transporter in the nucleus accumbens or striatum are involved in cocaine-induced behavioral sensitization by using in vivo electrochemistry to monitor the clearance of locally applied dopamine in anesthetized rats. Rats were injected with cocaine-HCl (10 mg/kg i.p.) or saline daily for 7 consecutive days and then withdrawn for 7 days. Pressure ejection of a finite amount of dopamine at 5-min intervals from a micropipette adjacent to the electrochemical recording electrode produced transient and reproducible dopamine signals. After a challenge injection of cocaine (10 mg/kg i.p.), the signals in the nucleus accumbens of cocaine-treated animals became prolonged and the clearance rate of the dopamine decreased, indicating significant inhibition of the dopamine transporter. In contrast, simultaneous measurements in the dorsal striatum indicated a transient increase in both the amplitude of the signals and the clearance rate of the dopamine. The signals in both brain regions in the saline-treated animals given the cocaine challenge were similar to those in untreated animals given an acute injection of cocaine (10 mg/kg i.p.) or saline. Behaviorally, not all of the cocaine-treated animals were sensitized; however, both sensitized and nonsensitized animals displayed similar changes in dopamine clearance rate. Quantitative autoradiography with [3H]mazindol revealed that the affinity of the dopamine transporter for cocaine and the density of binding sites were similar in cocaine- and saline-treated rats. The decrease in dopamine clearance rate observed in the nucleus accumbens of the cocaine-treated rats after a challenge injection of cocaine is consistent with increased dopaminergic transmission, but does not appear to be sufficient in itself for producing behavioral sensitization.

Animals↗
PubMed1993

Clearance of exogenous dopamine in rat dorsal striatum and nucleus accumbens: role of metabolism and effects of locally applied uptake inhibitors.

In vivo electrochemistry was used to investigate the mechanisms contributing to the clearance of locally applied dopamine in the dorsal striatum and nucleus accumbens of urethane-anesthetized rats. Chronoamperometric recordings were continuously made at 5 Hz using Nafion-coated carbon fiber electrodes. When a finite amount of dopamine was pressure-ejected at 5-min intervals from a micropipette adjacent to the electrode, transient and reproducible dopamine signals were detected. Substitution of L-alpha-methyldopamine, a substrate for the dopamine transporter but not for monoamine oxidase, for dopamine in the micropipette did not substantially alter the time course of the resulting signals. This indicates that metabolism of locally applied dopamine to 3,4-dihydroxy-phenylacetic acid is not responsible for the decline in the dopamine signal. Similarly, changing the applied oxidation potential from +0.45 to +0.80 V, which allows for detection of 3-methoxytyramine formed from dopamine via catechol-O-methyltransferase, had little effect on signal amplitude or time course. In contrast, lesioning the dopamine terminals with 6-hydroxydopamine, or locally applying the dopamine uptake inhibitors cocaine or nomifensine before pressure ejection of dopamine, significantly increased the amplitude and time course of the dopamine signals in both regions. The effects of cocaine and nomifensine were greater in the nucleus accumbens than in the dorsal striatum. Local application of lidocaine and procaine had no effect on the dopamine signals. Initial attempts at modeling resulted in curves that were in qualitative agreement with our experimental findings. Taken together, these data indicate that (1) uptake of dopamine by the neuronal dopamine transporter, rather than metabolism or diffusion, is the major mechanism for clearing locally applied dopamine from the extracellular milieu of the dorsal striatum and nucleus accumbens, and (2) the nucleus accumbens is more sensitive to the effects of inhibitors of dopamine uptake than is the dorsal striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Actions of A-75200, a novel catecholamine uptake inhibitor, on norepinephrine uptake and release from bovine adrenal chromaffin cells.

The balance between catecholamine (CA) release and reuptake is closely regulated and determines the effective level of transmitter at the synaptic cleft. Drugs that block CA uptake have potential utility as antidepressant medications. One such drug is racemic (+/-)-(1' R*,3R*)-3-phenyl-1-[1',2',3',4'-tetrahydro-5',6'- methylenedioxy-1'-naphthalenyl-methyl]-pyrrolidine methanesulfonate (A-7500), a novel polycyclic compound developed at Abbott Laboratories. This compound is known to bind to CA transporters in the central nervous system, however, its effects on an intact neurosecretory system have not been studied. In this regard, norepinephrine (NE) release from bovine adrenal chromaffin cells (BACC) is a classic model system for CA release and is an excellent system in which to examine the effects of drugs which modulate neurotransmitter release. We compared the effects of A-75200 and its two constituent enantiomers, A-74111 and A-74112, to the effects of three well-characterized uptake inhibitors, desipramine (DMI), nomifensine and cocaine. We found that the Abbott compounds inhibit [3H]norepinephrine ([3H]NE) uptake with an EC50 comparable to cocaine. In addition, unlike nomifensine and cocaine, these compounds inhibited nicotine- and K(+)-stimulated NE release, whereas histamine-stimulated release was preserved. Thus, the Abbott compounds block the effects on secretion of two agonists (nicotine and K+) which depend on a depolarization-dependent influx of extracellular calcium. We conclude that in addition to blocking NE uptake by inhibiting the NE transporter, the Abbott compounds may modulate peripheral NE release by inhibiting calcium flux through voltage-gated channels. This study demonstrates the utility of bovine adrenal chromaffin cells for preclinical trials of drugs that affect catecholaminergic neurotransmission.

Adrenal Medulla↗
PubMed1992

Human fetal xenografts of brainstem tissue containing locus coeruleus neurons: functional and structural studies of intraocular grafts in athymic nude rats.

Fetal human brainstem tissue including the nucleus locus coeruleus was transplanted to the anterior eye chamber of athymic nude rats. Most transplants survived and grew in the anterior chamber of the eye. After 9-15 months, the host animals were anesthetized and electrophysiological or in vivo electrochemical recordings were performed. The brainstem transplants contained spontaneously active neurons with regular single-spike firing patterns. The neurons responded to ipsilateral light stimulation with an increase in firing rate and to the alpha 2-receptor agonist clonidine with significantly decreased firing rates. In vivo electrochemical studies demonstrated reproducible noradrenergic overflow after local application of potassium. Immunohistochemical evaluation of the brainstem transplants showed an abundance of tyrosine hydroxylase-positive neurons and neurites in all transplants and a dense network of neurofilament-, synapsin-, and glial fibrillary acidic protein-positive profiles throughout the grafts. Taken together, the present physiological and histochemical data indicate that it is possible to obtain transplants containing a specific monoaminergic population within the brainstem from human fetal fragments and to maintain these transplants in oculo in athymic nude rats for at least 15 months, during which time noradrenergic neurons develop.

Animals↗
PubMed1992

Phencyclidine and auditory sensory gating in the hippocampus of the rat.

The psychotomimetic drug 1-(1-phenylcyclohexyl) piperidine (PCP, phencyclidine) was found to cause a deficit in the gating of the response of the hippocampal neuron to repeated auditory stimuli, which is similar to a particular physiological feature observed in human psychosis. Other drugs, with sigma agonist and/or N-methyl-D-aspartate (NMDA) antagonist effects, were administered and their ability to cause a loss of auditory gating was compared to that of PCP. The rank order of effectiveness was levoxodrol > PCP and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) > N-allylnormetazocine (SKF 10047) > dexoxodrol > 3-(+/-)2-carboxypiperazine-4-yl) propyl-1-phosphonate (CPP). Further studies of two of the drugs, PCP and MK-801, showed that selective lesioning of the noradrenergic input with the neurotoxin DSP4, as well as less selective depletion of monoamines with reserpine, blocked the loss of gating. Phencyclidine, and other drugs with the same spectrum of action, most likely disrupt gating by increasing noradrenergic activity through a sigma mechanism.

Acoustic Stimulation↗
PubMed1992

Differences in dopamine clearance and diffusion in rat striatum and nucleus accumbens following systemic cocaine administration.

Acute cocaine administration preferentially increases extracellular dopamine levels in nucleus accumbens as compared with striatum. To investigate whether a differential effect of cocaine on dopamine uptake could explain this observation, we used in vivo electrochemical recordings in anesthetized rats in conjunction with a paradigm that measures dopamine clearance and diffusion without the confounding effects of release. When a finite amount of dopamine was pressure-ejected at 5-min intervals from a micropipette adjacent to the electrode, transient and reproducible increases in dopamine levels were detected. In response to 15 mg/kg of cocaine-HCl (i.p.), these signals increased in nucleus accumbens, indicating significant inhibition of the dopamine transporter. The time course of the dopamine signal increase paralleled that of behavioral changes in unanesthetized rats receiving the same dose of cocaine. In contrast, no change in the dopamine signal was detected in dorsal striatum; however, when the dose of cocaine was increased to 20 mg/kg, enhancement of the dopamine signal occurred in both brain areas. Quantitative autoradiography with [3H]mazindol revealed that the affinity of the dopamine transporter for cocaine was similar in both brain areas but that the density of [3H]mazindol binding sites in nucleus accumbens was 60% lower than in dorsal striatum. Tissue dopamine levels in nucleus accumbens were 44% lower. Our results suggest that a difference in dopamine uptake may explain the greater sensitivity of nucleus accumbens to cocaine as compared with dorsal striatum. Furthermore, this difference may be due to fewer dopamine transporter molecules in nucleus accumbens for cocaine to inhibit, rather than to a higher affinity of the transporter for cocaine.

Animals↗
PubMed1992

Direct in vitro electrochemical measurement of dopamine overflow in intermediate pituitary: characterization and pharmacology.

The intermediate lobe of the pituitary (IL) is a promising model system for the study of dopaminergic neurotransmission. We sought to characterize the release of dopamine (DA) from the IL using electrochemical methods which provide increased spatial and temporal resolution compared to the superfusion techniques which had previously been employed to study this system. After pretreatment with monoamine oxidase (MAO) inhibitors, we were able to routinely measure DA overflow after 30-sec, 9-Hz electrical stimulation of the pituitary stalk. This effect was blocked by tetrodotoxin and Cd++ ions confirming that it was due to synaptic activation. Intracellular recording from the postsynaptic cells (melanotrophs) showed a postsynaptic hyperpolarization with a time course that was identical to that of DA overflow. Overflow was increased and prolonged by agents that inhibited DA uptake (nomifensine, mazindol or cocaine) and increased but not prolonged by a D2 antagonist (sulpiride), presumably acting via presynaptic autoreceptors. The DA precursor 3,4-dihydroxyphenylalanine also increased DA overflow gradually over a 45-min time period. In view of reports of possible colocalization of DA and gamma-aminobutyric acid in IL, we determined the possible effects of GABAergic agents on DA release. Neither agonists (muscimol or baclofen) nor antagonists (bicuculline or 2-hydroxysaclofen) had any effect on DA overflow. By using the MAOA-specific inhibitor clorgyline and the MAOB-specific inhibitor deprenyl we were able to confirm that the MAOA form of the enzyme is involved in DA metabolism in this preparation.

Animals↗
PubMed1992

Clearance and diffusion of locally applied dopamine in normal and 6-hydroxydopamine-lesioned rat striatum.

Studies of dopamine (DA) clearance and diffusion were carried out after unilateral destruction of striatal DA afferents using intraparenchymal injection of 6-hydroxydopamine (6-OHDA). Rats were screened for the extent of DA depletion by testing for contralateral rotations induced by 0.05 mg/kg of apomorphine. Exogenous DA clearance and diffusion were determined using rapid (5 Hz) in vivo chronoamperometry with Nafion-coated carbon-fiber electrodes. Local applications of DA by pressure ejection from micropipettes into the lesioned vs. nonlesioned striata, with dose adjusted to elicit roughly equivalent amplitudes of electroactive signals, manifested a much prolonged clearance time on the lesioned side. A second protocol involved administration of equal volumes (amounts) of DA into lesioned vs. nonlesioned striata. In such cases, a volume of DA which manifested no detectable signal on the intact side produced a pronounced electrochemical signal on the lesioned side. When nomifensine, a high-affinity DA uptake inhibitor, was locally applied into the intact striatum, a subsequent ejection of DA produced a much larger signal than when the same volume was given before nomifensine. Very little or no effects of nomifensine were seen in 6-OHDA-lesioned striata. Taken together, these data indicate a much prolonged clearance time of DA in 6-OHDA-denervated striata. Moreover, the data also suggest that the primary mechanism underlying this effect is the loss of high affinity neuronal uptake. Thus, such changes in DA clearance may help account for some of the well documented compensatory phenomena which occur after DA-depleting lesions in animals and in man.

Animals↗
PubMed1991

Electrically-evoked release of norepinephrine in the rat cerebellum: an in vivo electrochemical and electrophysiological study.

Norepinephrine (NE) release from the locus coeruleus (LC) afferents to the cerebellar cortex of urethane anesthetized rats was achieved by electrical stimulation of the locus coeruleus or by local administration of potassium into the cerebellum. Both methods evoked an overflow of NE-like electroactive species. Electrically-evoked and potassium-induced overflow of NE-like responses were found to be reversible and reproducible. Releases were not observed in cerebellar white matter, an area which is relatively devoid of monoamine containing terminals. Systemic administration of desipramine, a potent and selective norepinephrine re-uptake blocker, significantly augmented the electrically-evoked electrochemical responses. Measurements of evoked release taken using high-speed chronoamperometry support the idea that a predominant contributor to electrically-induced signals was NE. Electrophysiological recordings of single Purkinje cells were performed with the same Nafion-coated single carbon fiber electrodes used for electrochemical recordings. Electrical stimulation of the LC was seen to depress Purkinje cell firing rates; an increase in electroactive species was detected at the same site that paralleled the time course of the electrophysiological response. These studies provide further direct evidence that the LC norepinephrine-containing cells have a direct inhibitory effect on Purkinje cells in the cerebellum, and that both pre- and postsynaptic events can be measured with the same recording sensor.

Animals↗
PubMed1991

Function of intraventricular human mesencephalic xenografts in immunosuppressed rats: an electrophysiological and neurochemical analysis.

Solid pieces of human fetal mesencephalic tissue were grafted to the lateral ventricle adjacent to dopamine-depleted striata of rats immunosuppressed with cyclosporin A. Apomorphine-induced rotations were performed before and at monthly intervals after grafting. Reductions in rotations were seen at 2 months post-grafting and these reductions progressively increased. Spontaneously active dopaminergic cells were found within the grafts using extracellular single-unit recording techniques. Recordings of striatal cells ipsilateral to the graft revealed "normal" firing rates compared to those of neurons in the control striatum. In response to the local application of the dopamine antagonist cis-flupenthixol, both the dopaminergic and striatal neurons showed dose-dependent excitations. Potassium-evoked releases of electroactive species ipsilateral to the fetal human graft, measured using high-speed in vivo electrochemistry, revealed response amplitudes that were similar to control striatum when an electrode was placed adjacent to the graft; distal to the graft the responses showed smaller amplitudes but prolonged time courses. Much greater levels of dopamine and serotonin were detected in the grafts, compared to in normal rat substantia nigra, as measured with HPLC coupled to a 16-channel electrochemical array detector. Immunocytochemical studies using antibodies against tyrosine hydroxylase (TH), revealed not only TH-positive cells within the graft, but also a few positive neurons that migrated into the host striatum. Numerous TH-immunoreactive fibers penetrated into striatum and reinnervated its total volume. Taken together, these data suggest that intraventricular graft placement may be a highly efficacious technique for studying fetal brain tissues in terms of maturation, reinnervation, and function.

Analysis of Variance↗
PubMed1991

Effects of dopamine receptor agonists and antagonists on catecholamine release in bovine chromaffin cells.

Dopamine D2 receptors are known to regulate the release of catecholamines from neurons in the central and peripheral nervous systems. In the present study we have evaluated the effects of dopamine D2 agonists and antagonists on the release of endogenous norepinephrine and epinephrine stimulated by 50 microM nicotine in isolated bovine chromaffin cells in order to investigate whether isolated bovine chromaffin cells may contain functional dopamine D2 receptors. Dopamine (10(-4) and 10(-6) M), quinpirole (10(-5) M) and 2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (10(-5) M) had no effect on the nicotine-stimulated release of norepinephrine or epinephrine from the bovine chromaffin cells. Pergolide (10(-6) M) and apomorphine (10(-4) M) produced a significant inhibition of nicotine-stimulated release of both norepinephrine and epinephrine from the chromaffin cells. The inhibitory effect of the selective dopamine D2 agonist pergolide on catecholamine release from the chromaffin cells was not reversed by 10(-6) M concentrations of the selective dopamine D2 receptor antagonists haloperidol, domperidone, metaclopramide, fluphenazine, flupentixol, (+)- or (-)-sulpiride, the dopamine D1 receptor antagonist SCH 23390 (10(-7) M) or the alpha receptor antagonist phentolamine (10(-6) M). These data suggest that the inhibition of nicotine-stimulated release of catecholamines from the bovine chromaffin cells is not a receptor-mediated effect. Further studies showed that the inhibitory effect of pergolide on catecholamine release in the bovine chromaffin cells was correlated with an inhibition of nicotine-stimulated 45Ca++ uptake and 22Na+ uptake into these cells. It is concluded that functional dopamine D2 receptors of the classical type do not exist on isolated bovine chromaffin cells.

Animals↗