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F Vaccarino

Publications and source records attributed to F Vaccarino.

At least 19 recordsLinked to original sources
PubMed2001

Analysis of amino acids and catecholamines, 5-hydroxytryptamine and their metabolites in brain areas in the rat using in vivo microdialysis.

In vivo microdialysis, using dialysis probes inserted into discrete brain areas and subsequent analysis of neurotransmitters and related substances in the dialysates (usually with HPLC), has yielded a great deal of important information about the actions of psychotropic drugs and endogenous neurotransmitter systems and about the functional interactions between various brain areas. This paper reviews the principles involved in in vivo microdialysis, its advantages and disadvantages, and recent innovations in methodology and applications. The first section includes brief discussions of principles and applications of dialysis, use of anesthetized versus conscious freely moving animals, and methods used to determine the neural origin of neurotransmitters in the dialysate. The subsequent sections provide detailed descriptions, based largely on our own studies in rats, of stereotaxic surgery, in vivo microdialysis, and dialysate analysis, with an emphasis on amino acids and biogenic amines and their metabolites. A discussion of methodological problems which may be encountered in the analysis of amino acids and biogenic amines is also included.

Amino Acids↗
PubMed2000

Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in rats.

RATIONALE: Human positron emission tomography (PET) shows that striatal dopamine D2 receptor occupancy predicts extrapyramidal side effects (EPS). Patients showed a clinical response with > or = 65% D2 occupancy, but EPS only when D2 occupancy >78%. Catalepsy and the selective suppression of conditioned avoidance response (CAR) are often used as animal models to predict EPS and antipsychotic effect, respectively. However, the quantitative relationship between striatal D2 occupancy and effects in these models is not known. OBJECTIVES: The present study intended to investigate the relationship between animal catalepsy, suppression of CAR, and D2 receptor blockade using a method of evaluating D2 receptor occupancy similar in principle to that used in patients. METHODS: In vivo binding of [11C]-raclopride and [3H]-raclopride was compared. Doses of cold raclopride were chosen to provide a D2 occupancy from 0 to 95%. The relationship between dose/time course of catalepsy and D2 occupancy was assessed. Effects of raclopride on conditioned avoidance response (CAR) behavior were tested. RESULTS: In vivo binding of [11C]-raclopride compared to [3H]-raclopride was virtually the same. Using [3H]-raclopride, cold raclopride (0.01-0.2 mg/kg) produced 16-77% D2 receptor occupancy and no catalepsy. Raclopride (0.5-2 mg/kg) produced 83-95% D2 occupancy and significant catalepsy. Raclopride (2 mg/kg) produced on average 95% and 87% D2 receptor occupancy 1 and 2 h after administration, respectively, and maximum catalepsy. D2 occupancy at 4, 8 and 24 h was on average 58%, 46%, and 4%, respectively. No catalepsy was observed. Raclopride (0.2 mg/kg), estimated at 70-75% D2 occupancy, produced suppression of CAR. CONCLUSIONS: In vivo D2 occupancy measurements in rats using [3H]-raclopride is analogous to using [11C]-raclopride in human PET scanning. Suppression of CAR occurred at a D2 occupancy of around 70-75%, and catalepsy at D2 occupancy >80%. Results closely resembled human studies where 65-70% D2 occupancy was required for antipsychotic response, while > or = 80% D2 occupancy led to EPS. Brain mechanisms involved in mediation of catalepsy in rats and EPS in humans might indeed be similar. Both suppression of CAR in rats and antipsychotic response in humans might share an underlying construct, i.e. the need for around 70% D2 receptor blockade.

Animals↗
PubMed2000

Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling.

Glucagon-like peptide-1 (GLP-1), a potent regulator of glucose homeostasis, is also produced in the central nervous system, where GLP-1 has been implicated in the neuroendocrine control of hypothalamic-pituitary function, food intake, and the response to stress. The finding that intracerebroventricular GLP-1 stimulates LH, TSH, corticosterone, and vasopressin secretion in rats prompted us to assess the neuroendocrine consequences of disrupting GLP-1 signaling in mice in vivo. Male GLP-1 receptor knockout (GLP-1R-/-) mice exhibit reduced gonadal weights, and females exhibit a slight delay in the onset of puberty; however, male and female GLP-1R-/- animals reproduce successfully and respond appropriately to fluid restriction. Although adrenal weights are reduced in GLP-1R-/- mice, hypothalamic CRH gene expression and circulating levels of corticosterone, thyroid hormone, testosterone, estradiol, and progesterone are normal in the absence of GLP-1R-/- signaling. Intriguingly, GLP-1R-/- mice exhibit paradoxically increased corticosterone responses to stress as well as abnormal responses to acoustic startle that are corrected by glucocorticoid treatment. These findings suggest that although GLP-1R signaling is not essential for development and basal function of the murine hypothalamic-pituitary-adrenal axis, abrogation of GLP-1 signaling is associated with impairment of the behavioral and neuroendocrine responses to stress.

Acoustic Stimulation↗
PubMed1988

Subsets of GABAergic neurons in dissociated cell cultures of neonatal rat cerebral cortex show co-localization with specific modulator peptides.

The GABAergic properties of dissociated neurons from cerebral cortex of neonatal rats were studied in primary culture using electrophysiological, biochemical and immunohistochemical methods. Cultured neurons had a resting potential of -50 to -60 mV and exhibited spontaneous excitatory and inhibitory synaptic currents. Non-spontaneous (elicited) ionic currents were produced by direct application of GABA and glutamate. Cultures contained measurable amounts of GABA from the first day in culture; GABA content reached a plateau around the 10th day of culture, and continued, nearly unchanged, until the 21st day of culture. Immunohistochemistry showed that 45% of the total cells in culture contained glutamic acid decarboxylase (GAD). Octadecaneuropeptide (ODN), a putative neuroregulatory peptide for benzodiazepine recognition sites, was present in approximately 28% of all neurons. Ninety-three percent of ODN-positive cells demonstrated GABAergic properties as well by displaying GAD-immunoreactivity. The peptide GABA-modulin (GM), a putative GABA receptor modulator, was found in about 75% of all neurons, with a further 65% of these cells exhibiting GAD-immunoreactivity. Cells immunopositive for neuropeptide Y (NPY), somatostatin (SRIF), and cholecystokinin-octapeptide (CCK), were found at much lower incidence (1-4%). Double-labelling studies showed that 90-97% of the cells positive for NPY, SRIF and CCK were also positive for GAD. Cells immunoreactive with serotonin or tyrosine hydroxylase were not detected. We suggest that primary cultures of neonatal cortical neurons may provide a useful experimental model to investigate the function and the modulation of GABAergic neurotransmission in the cerebral cortex.

Animals↗
PubMed1987

Ganglioside inhibition of glutamate-mediated protein kinase C translocation in primary cultures of cerebellar neurons.

In primary cultures of cerebellar granule cells, protein kinase C (PKC) translocation and activation can be triggered by the stimulation of excitatory amino acid neurotransmitter receptors. Glutamate evokes a dose-related translocation of 4-beta-[3H]phorbol 12,13-dibutyrate ([3H]-P(BtO)2) binding sites from the cytosol to the neuronal membrane and stimulates the incorporation of 32P into a number of membrane proteins, particularly protein bands in the range of 80, 50, and 40 kDa. The glutamate-evoked PKC translocation is Mg2+ sensitive, is prevented by 2-amino-5-phosphonovalerate and phencyclidine, is not inhibited by nitrendipine (a voltage-dependent Ca2+-channel blocker) but is abolished by the removal of Ca2+ from the incubation medium, suggesting that glutamate-mediated Ca2+ influx is operative in the redistribution of PKC. Exposure of granule cells to the gangliosides trisialosylgangliotetraglycosylceramide (GT1b) or monosialosylgangliotetraglycosylceramide (GM1) inhibits the translocation and activation of PKC evoked by glutamate. These glycosphingolipids fail to interfere with glutamate binding to its high-affinity recognition site or with the [3H]P(BtO)2 binding, nor do they affect the Ca2+ influx. These gangliosides may prevent PKC translocation by interfering with the PKC binding to the neuronal membrane phosphatidylserine.

Animals↗
PubMed1987

Subcellular location and neuronal release of diazepam binding inhibitor.

Diazepam binding inhibitor (DBI), a peptide located in CNS neurons, blocks the binding of benzodiazepines and beta-carbolines to the allosteric modulatory sites of gamma-aminobutyric acid (GABAA) receptors. Subcellular fractionation studies of rat brain indicate that DBI is compartmentalized. DBI-like immunoreactivity is highly enriched in synaptosomes obtained by differential centrifugation in isotonic sucrose followed by a Percoll gradient. In synaptosomal lysate, DBI-like immunoreactivity is primarily associated with synaptic vesicles partially purified by differential centrifugation and continuous sucrose gradient. Depolarization induced by high K+ levels (50 mM) or veratridine (50 microM) released DBI stored in neurons of superfused slices of hypothalamus, hippocampus, striatum, and cerebral cortex. The high K+ level-induced release is Ca2+ dependent, and the release induced by veratridine is blocked by 1.7 microM tetrodotoxin. Depolarization released GABA and Met5-enkephalin-Arg6-Phe7 together with DBI. DBI is also released by veratridine depolarization, in a tetrodotoxin-sensitive fashion, from primary cultures of cerebral cortical neurons, but not from cortical astrocytes. Depolarization fails to release DBI from slices of liver and other peripheral organs. These data support the view that DBI may be released as a putative neuromodulatory substance from rat brain neurons.

Animals↗
PubMed1985

GABA-modulin: a synaptosomal basic protein that differs from small myelin basic protein of rat brain.

GABA-modulin, a basic protein that allosterically inhibits the high-affinity binding of GABA to its recognition sites, has been extracted and purified from the synaptosomal fraction of rat brain where it represents approximately 0.5% of the total synaptosomal proteins. GABA-modulin has characteristics in common to the class of highly basic proteins isolated from myelin, in particular to the rat small myelin basic protein (SMBP). However, GABA-modulin is located selectively in synaptosomes, whereas the SMBP is located in myelin. Moreover, synaptosomal GABA-modulin is different from SMBP in amino acid composition (it contains more Glx and Lys and fewer Arg residues) and in apparent molecular weight (17,000 and 15,000 for GABA-modulin and SMBP, respectively). Synaptosomal GABA-modulin fails to bind [3H]muscimol per se but noncompetitively inhibits (IC30 approximately 0.5 microM) the binding of [3H]muscimol to purified synaptic membranes. Cyanogen bromide treatment generated a 13,000 MW major fragment from both SMBP and GABA-modulin. These two fragments were compared and showed differences in amino acid composition and sequence. Moreover, the peptide maps generated from GABA-modulin and SMBP by trypsin and staphylococcal V8 protease digestion are different. The high concentration of GABA-modulin in synaptosomal membranes, its high potency in the inhibition of GABA binding, and its neuronal specificity suggest that GABA-modulin plays an important role in neuronal membrane function linked to the modulation of GABA and perhaps other neurotransmitter receptors.

Amino Acids↗
PubMed1985

gamma-Aminobutyric acid- and benzodiazepine-induced modulation of [35S]-t-butylbicyclophosphorothionate binding to cerebellar granule cells.

t-Butylbicyclophosphorothionate (TBPS) is a bicyclophosphate derivative with potent picrotoxin-like convulsant activity that binds with high affinity and specificity to a Cl- channel-modulatory site of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Using intact cerebellar granule cells maintained in primary culture, we have studied the modifications induced by GABA and diazepam on the ion channel-modulatory binding site labeled by [35S]TBPS. At 25 degrees C, and in a modified Locke solution, the [35S]TBPS specific binding, determined by displacing the radioligand with an excess (10(-4) M) of picrotoxin, was approximately 70% of the total radioactivity bound to the cells. [35S]TBPS specific binding was saturable with a Kd of approximately 100 nM, a Bmax of approximately 440 fmol/mg of protein, and a Hill coefficient of 1.18. Neither cerebellar astrocytes maintained in culture for 2 weeks nor a neuroblastoma cell line (NB-2A) exhibited any specific [35S]TBPS binding. Muscimol (0.3 to 5 microM) enhanced and bicuculline (0.1 to 5 microM) inhibited [35S]TBPS specific binding to intact cerebellar granule cells. The effect of muscimol and bicuculline on [35S]TBPS binding was noncompetitive. Muscimol (0.1 to 5 microM) reversed bicuculline inhibition in a dose-dependent fashion but failed to reverse picrotoxin-induced inhibition. [35S]TBPS binding was also modulated by benzodiazepine receptor ligands. The binding was increased by diazepam and decreased by 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methylester. Muscimol (0.05 microM) failed to reverse bicuculline inhibition in the absence of diazepam, but it became effective in the presence of 0.1 to 1 microM diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

In vivo modulation of brain dopamine recognition sites: a possible model for emission computed tomography studies.

The content of authentic 3H-spiroperidol and of its metabolites was measured in brain regions of rat, guinea pig and mouse receiving tracer doses of 3H-spiroperidol intravenously (0.2 to 0.5 micrograms/kg). The time course of the 3H-spiroperidol content of various brain regions shows that a steady state was maintained between 2 and 6 hrs; the lowest 3H-spiroperidol content was attained in cerebellum where the value approached that of blood plasma. Since the cerebellum contains an insignificant number of dopamine receptors but many serotonin receptors and other sites that bind 3H-spiroperidol, the 3H-spiroperidol contained in cerebellum was considered background binding. In the striatum and olfactory tubercle of rats receiving two daily doses for 3 weeks of haloperidol or amphetamine the amount of 3H-spiroperidol that binds in vivo is decreased or increased, respectively. If the kinetic characteristics of in vivo binding of 3H-spiroperidol observed in the rat, guinea pig and mouse can be replicated in man using spiroperidol containing a gamma- or a position-emitting label, one might have a probe to study dopamine receptors in vivo with emission computed tomography scanning.

Animals↗
PubMed1983

GABAergic synapses. Supramolecular organization and biochemical regulation.

Extraneurally released gamma-aminobutyric acid (GABA) interacts with specific recognition sites associated with proteins located in postsynaptic neuronal membranes that function as chloride (Cl-)ionophores. As a result of the interaction between GABA and the recognition sites, Cl- ionophores are opened causing an influx or an efflux of Cl-, depending on the values of the Cl- equilibrium potential and of the membrane potential. Hyperpolarization or depolarization will result from inward or outward Cl- fluxes, respectively. Independently of the change in conductivity elicited by GABA, this amino acid transmitter will reduce the effectiveness of the sodium ion (Na+) excitatory potential. In attempts to elucidate the molecular mechanism, whereby benzodiazepines facilitate the action of GABA on membrane conductance without changing the activity of Cl- or other ionophore, a basic protein (GABA-modulin, GM) has been isolated from rat brain which is similar in structure to the small molecular weight myelin basic protein, found in rodent brain. While GABA-modulin is located in synaptosomes, the small molecular weight myelin basic protein is located in the myelin fraction: more important, GABA-modulin inhibited the high affinity binding of GABA to crude synaptic membranes while the basic myelin protein did not. Also, amino acid composition and molecular weight differentiate the two proteins. The GABA-modulin can be phosphorylated with different stoichiometry by cyclic AMP-dependent protein kinase (4 mol PO4(-3)) or Ca2+-dependent protein kinase (1 mol PO4(-3)). Only cyclic AMP-dependent phosphorylation inhibited the action of GABA-modulin on GABA binding.

Animals↗
PubMed1982

Self-stimulation and circling reveal functional differences between medial and lateral substantia nigra.

Functional differences between medial and lateral substantia nigra (SN) sites mediating intracranial self-stimulation (ICSS) and circling behaviours were explored. It was found that, for medial SN stimulation sites, D- and L-amphetamine (1 mg/kg) had equipotent, slightly facilitatory effects on ICSS rates while for lateral SN stimulation sites, D-amphetamine increased and L-amphetamine decreased ICSS rates. It is suggested that these effects may be due to medial and lateral dopamine cells having different sensitivities to amphetamine isomers. Imposed continuous stimulation of the ICSS sites induced contralateral circling from the medial SN placements and ipsilateral circling from the lateral SN placements. In rats receiving lesions through the ICSS electrode, D-amphetamine (2 mg/kg) induced ipsilateral circling following medial SN damage and contralateral circling after lateral SN damage. These results suggest that lateral and medial SN mechanisms of ICSS and circling differ, and that the lateral SN may be antagonistic to medial SN mechanisms involved in circling behaviour.

Amphetamine↗
PubMed1981

Complications in surface replacement arthroplasty of the hip: experience with the Paltrinieri-Trentani prosthesis.

A method of surface replacement arthroplasty of the hip joint is described for use in selected patients, often in the younger age group. One hundred and forty patients were reviewed after a mean interval of four years. Seventy-two per cent were graded 5 or 6 on the Charnley scale, the remainder had symptoms due to femoral neck fracture or loosening of the prosthetic components. In the main the bad results were attributed to incorrect patient selection or technical imperfections with the operative technique. The advantages of the operation are no alteration in the relationship of the femoral head, neck and acetabulum and minimal interference with the surrounding muscle and soft tissues. The amount of implanted material is reduced and no entry is made into the femoral medullary canal, which facilitates any further revision surgery that may be necessary.

Adult↗
PubMed1979

Vomeronasal and olfactory system modulation of maternal behavior in the rat.

The onset of maternal responsiveness by virgin female rats to foster pups was observed after (i) complete vomeronasal nerve cuts, (ii) partial olfactory bulb cuts, or (iii) the combined procedures. Although both vomeronasal nerve cuts and olfactory bulb cuts resulted in a more rapid onset of maternal care, relative to control animals with sham operations, animals sustaining the loss of both sources of olfactory input exhibited the shortest response latency. These findings are discussed in terms of the probable distinct functions of the two olfactory systems in the control of maternal behavior in the rat.

Afferent Pathways↗
PubMedDate not supplied

The Paltrinieri-Trentani hip joint resurface arthroplasty.

The Paltrinieri-Trentani type of resurfacing the hip has been under clinical investigation for over 6 years. The prostheses consist of a metal cap, which is fitted to the head of the femur (no amputation of the neck and the head being required) and an acetabular cup made of high density polyethylene. Matched cups and caps are available in different sizes. The biomechanical preconditions upon which this hip resurfacing is based must be understood to successfully perform the operation. The series of patients reported here were aged between 32 and 70 years. The results after 6 years are 76% successful, and typical cases rate between 5 and 6 on the Charnley Scale; 12% rated between 3 and 4; 12% were failures owing either the fracture of the neck of the femur or to loosening of the femoral prosthesis. Further analysis of the cases demonstrated that: prostheses applied with the correct surgical technique gave satisfactory results; failures were attributable to errors of technique and indication.

Arthroplasty↗