Biomedical subjects

D B Gilbert

Publications and source records attributed to D B Gilbert.

At least 19 recordsLinked to original sources

PubMed1995

The putative dopamine D3 agonist, 7-OH-DPAT, reduces dopamine release in the nucleus accumbens and electrical self-stimulation to the ventral tegmentum.

The present experiments were designed to test further the idea that 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin), a putative dopamine (DA) D3 agonist, has effects at DA autoreceptors to reduce intracranial DA levels and to reduce behaviours that are DA-dependent. Rats were trained to respond on a self-stimulation protocol for electrical stimulation to the ventral tegmental area (VTA). Each press of a lever delivered a 0.5 s train of square wave, 1.5 ms duration, 100 Hz, 90-120 mA stimulation. Systemic administration of 7-OH-DPAT at 0.01-0.3 mg/kg i.p., quickly dose-dependently reduced responding. Electrical stimulation using similar parameters to those that supported self-stimulation were then applied to the VTA of anaesthetized rats. Fast cyclic voltammetry (FCV) revealed that this stimulation released DA in the nucleus accumbens (NAC). 7-OH-DPAT i.p. (0.1-3.0 mg/kg) quickly and potently reduced the size of the DA-generated voltammetric signal. This effect of 0.3 mg/kg 7-OH-DPAT was not blocked by sulpiride (60 mg/kg, i.p.) a D2-specific antagonist that may preferentially block D2 autoreceptors. These data are discussed with reference to the possibility that 7-OH-DPAT reduces the release of dopamine in the NAC, at D3, but not at D2, autoreceptors and that this in turn may reduce the rewarding effect of VTA stimulation.

Animals↗

PubMed1995

Dopamine receptor subtype agonists and feeding behavior.

Stimulation or blockade of various dopamine receptor subtypes is associated with reduced feeding. For example, D2 receptor agonists suppress feeding in food-deprived and free-feeding rats, and in rats given access to a highly palatable diet. Similarly, reduced food intake is associated with the actions of diverse D1 receptor agonists, and these compounds can interact synergistically with D2 receptor agonists to potentiate reductions in feeding. Using microstructural analysis to compare D1 and D2 agonist effects, specific differences emerge in their modes of action. D1 agonists reduce the duration of feeding, primarily by decreasing the frequency of feeding bouts, whereas D2 agonists reduce the local rate of eating. However, since D1 agonists uniquely reduce feeding in the absence of other behavioral impairments and are less disruptive of the pattern of feeding behavior, it has been suggested that D1 agonists are more likely than D2 agonists to act on central mechanisms regulating food intake. Moreover, only D1 agonists are effective in suppressing sucrose sham-feeding, suggesting that D1 receptor stimulation may promote satiety. Nevertheless, many questions remain. For example, antagonist studies have implicated 5-HT receptor stimulation in the anorectic effects of D1 agonists, suggesting that further pharmacological and behavioral analyses of receptor-subtype agonist effects are required. Above all, recent developments in the classification of dopamine receptor subtypes reveal the need for new studies examining the involvement of D3, D4 and D5 receptors in feeding.

Animals↗

PubMed1995

7-OH-DPAT injected into the accumbens reduces locomotion and sucrose ingestion: D3 autoreceptor-mediated effects?

7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) injected bilaterally in the nucleus accumbens (NAC) resulted in profound, noncatatonic, dose-dependent (0.3-3 mg total dose) hypolocomotion but without inducing yawning. It also decreased intake of a highly preferred 3% sucrose solution (1 microgram total dose). Systemic injection of 7-OH-DPAT (0.1-3.0 mg/kg, i.p.) similarly induced hypolocomotion while failing to induce yawning. In none of these studies did rats show any signs of hyperlocomotion or any stereotyped responses normally associated with D2 or mixed D1/D2 receptor stimulation. These data suggest that hypolocomotion elicited by 7-OH-DPAT in the NAC may be mediated at the D3 receptor as distinct from the D2 dopamine receptor. We discuss the possibility that the behavioural effects we observed are mediated at D3 autoreceptors.

Animals↗

PubMed1995

Analysis of condylar position change on digitally subtracted Orthophos P-4 and Sectograph zonogram images.

The purpose of this study was to compare the accuracy of two single-image techniques that provide parasagittal views of the temporomandibular joint. Orthophos program 4 and Sectograph zonographic techniques were evaluated using digital subtraction to measure 1-, 2-, and 3-mm shifts of condylar position in horizontal or vertical planes. Precise repositioning of a human skull was facilitated by laser alignment beams. Statistically significant differences between radiographic techniques reflected the tendency for overestimating of shifts with program 4 and underestimation with zonographic techniques. Pooled mean difference values were 0.12 mm for program 4 images of -0.17 mm for zonograms. Program 4 images and zonograms produced with precise repositioning of anatomy approached the accuracy of tomograms and may prove useful for evaluating parasagittal alterations in condylar position in pretreatment and posttreatment radiographs.

Analysis of Variance↗

PubMed1994

Analysis of condylar position changes: a test of validity of posteroanterior cephalometric and 20-degree lateral cephalometric techniques enhanced by digital subtraction.

This preclinical study was designed to evaluate 20-degree lateral cephalometric and posteroanterior cephalometric techniques with digital subtraction enhancement for their ability to detect 1-, 2-, and 3-mm shifts in condylar position in two of three planes of space (horizontal or transverse and vertical). The model used was a dry human skull with a complete mandible mounted on a microscopic stage with positioning accuracy to 0.1 mm in x, y, and z planes. Analysis of variance showed no significant difference from expected values in the transverse plane (posteroanterior cephalogram only). There were significant differences in the sagittal plane (20-degree lateral cephalogram only) for the 2- and 3-mm shifts (P < .001). There were no significant differences among expected values in the vertical plane for individual increments or for increment comparisons. The magnitude of standard deviations and of the absolute value of differences indicates markedly increased variability for both techniques as compared to tomograms produced with cephalostat repositioning. The authors conclude that even with precise repositioning and digital subtraction enhancement, cephalometric radiographs are inadequate for clinical monitoring of condylar position.

Analysis of Variance↗

PubMed1993

The selective 5-HT3 receptor antagonist, ondansetron, augments the anorectic effect of d-amphetamine in nondeprived rats.

Previous behavioural studies have shown that 5-hydroxytryptamine3 (5-HT3) receptor antagonists either block or have no effect on amphetamine-induced effects. The present experiments investigated whether or not the highly selective 5-HT3 receptor antagonist ondansetron would affect the anorectic effect of a small dose (1 mg/kg) of d-amphetamine. Nondeprived male rats were tested in two feeding paradigms: consumption of a palatable sweetened mash and ingestion of a 3% sucrose solution. Ondansetron (10-100 micrograms/kg) did not antagonize amphetamine-induced anorexia; instead, in both paradigms consumption was reduced still further when the 5-HT3 antagonist was given in conjunction with amphetamine. Ondansetron given alone had significant effects on consumption, but the direction of the effect differed according to the paradigm. Sweetened mash intake was significantly increased at 30 and 100 micrograms/kg, while sucrose ingestion was significantly reduced at 10 and 30 micrograms/kg ondansetron. It is suggested that ondansetron has two opposing effects on intake, one of which (hyperphagia) can be masked by d-amphetamine, leaving an anorectic effect that augments that of d-amphetamine.

Animal Feed↗

PubMed1991

Dissociation of brain sites necessary for registration and storage of memory for a one-trial passive avoidance task in the chick.

Although memory formation occurs in a sequence of pharmacologically dissociable stages, many models assume that this sequence is located within a single neuronal ensemble. Three forebrain areas in the young chick-the intermediate medial hyperstriatum ventrale (IMHV), the lobus parolfactorius (LPO), and the paleostriatum augmentatum--have been identified as important structures in mediating learning and memory processes. It has been shown that pretraining lesions placed to the left IMHV produce amnesia for a 1-trial passive avoidance task. Posttraining lesions in the IMHV are not amnestic. The present study demonstrated that bilateral lesions to the LPO are amnestic but only if made subsequent to rather than before training. These results suggest that long-term storage of the memory is dependent on the LPO. Further experiments determined that in the absence of the LPO at training, the right IMHV can act a long-term memory storage site. In the absence of the right IMHV at training, other, as yet undetermined, areas can take up this role.

Afferent Pathways↗

PubMed1990

Pre- and post-training lesions of the intermediate medial hyperstriatum ventrale and passive avoidance learning in the chick.

Three distinct nuclei of the chick forebrain--the intermediate medial hyperstriatum ventrale (IMHV), lobus parolfactorius (LPO), and paleostriatum augmentatum (PA)--show metabolic, morphological, and neurophysiological changes following training on a passive avoidance task, suggesting that these and other areas of the chick forebrain participate in memory formation for this task. Considerable evidence exists for lateralization of memory processes in the chick. Several experiments examined the effects of lesions in the IMHV on the ability of chicks to learn and retain the avoidance task. Pre-training bilateral lesions in the IMHV produced an impairment in avoidance responding tested three hours after training. Pre-training unilateral lesions in the left but not the right IMHV resulted in a similar impairment. However, bilateral IMHV ablations, given either 1 or 6 h post-training, did not impair retention. IMHV lesions did not impair retention of a simple escape learning task. These results are consistent with other studies that have examined the effects of bilateral IMHV lesions on acquisition of passive avoidance and extend these findings by demonstrating lateralization of acquisition involving the left IMHV. The results also suggest that, as early as one hour post-training, the IMHV is not necessary to retain the memory and indicate that other forebrain structures, possibly the LPO or PA, may maintain the memory trace following training. Hypotheses to account for these results and indications of future research are discussed.

Animals↗

PubMed1989

Opposite effects of SK&F 38393, a dopamine D-1 agonist, and SCH 23390, a dopamine D-1 antagonist, in tests of salt preference/aversion in the rehydrating rat.

Male rats were adapted to a 22-hr water-deprivation schedule, and to a 15-min choice test, in which water was available in one drinking tube, and water, 0.064%, 0.16%, 0.4%, 1.0%, or 2.5% NaCl solution, respectively, was available in a second. A typical saline preference-aversion function was obtained. The selective dopamine D-1 agonist, SK&F 38393 (3.0 mg/kg, IP), significantly depressed choice of hypertonic saline solutions (1.0% and 2.5% NaCl solutions), without affecting preference for hypotonic saline solutions. In contrast, the selective dopamine D-1 antagonist, SCH 23390 (0.1 mg/kg, SC), significantly increased the preference measure in the case of hypertonic solutions. These data indicate a role for D-1 receptors in dopaminergic mediation of the descending limb of the saline preference-aversion function.

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

PubMed1989

Midazolam induces amnesia in a simple, one-trial, maze-learning task in young chicks.

We report a simple, one-trial, learning paradigm which we have developed for use in young chicks. Chicks were separated from their brood mates and placed in a small isolation chamber. A 'T' corridor, or maze, connected the isolation chamber to the brood space, allowing the chick to escape isolation stress and rejoin the brood. When the chick successfully negotiated the corridor, the latency to perform this task was recorded. On a subsequent trial, any improvement in the speed of performance was reasoned to reflect the chick's memory of the task. Undrugged chicks always showed significant improvement in task latency if they were replaced in the maze 3 hours after a successful escape, suggesting that they had remembered the task. Chicks given midazolam (0.1 or 0.3 mg/kg, IP), a benzodiazepine, before the first escape, showed no improvement on their second escape. Improved performance was seen, however, if a second injection of midazolam was given before the second escape, suggesting a state-dependent effect.

Amnesia↗

PubMed1987

Effects of the dopamine D-1 antagonist SCH 23390 and the D-2 antagonist sulpiride on saline acceptance-rejection in water-deprived rats.

Separate groups of water-deprived rats were familiarized with drinking water or one of a range of NaCl solutions (0.45-2.7%) in a 30 min test. The substituted benzamide, sulpiride, a selective dopamine D-2 receptor antagonist, significantly increased the consumption of water and hypotonic saline at 30 mg/kg. In contrast, the selective dopamine D-1 receptor antagonist, SCH 23390 (0.01-0.1 mg/kg SC) significantly reduced the intake of water and of saline at different concentrations in a dose-dependent manner. Consumption of water and 0.45% saline were most sensitive to the antidipsogenic effect of SCH 23390. These results suggest that previously-reported antidipsogenic effects of neuroleptics may depend, to at least some degree, on dopamine D-1 receptor blockade. The increase in drinking produced by sulpiride indicates that dopamine may act at D-2 receptors to inhibit the consumption of water and hypotonic saline, but not of stronger salt solutions.

Animals↗

PubMed1987

Internist's lament.

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Hospital Records↗

PubMed1986

Naloxone antagonizes the hyperdipsic effect of sulpiride in a salt-preference test in male and female rats.

The consumption of saline and water in a two-bottle test of salt-preference was measured after the administration of sulpiride, a dopamine receptor antagonist and of naloxone, an antagonist at opiate receptors. The two drugs were injected alone, or in combination. Three concentrations of saline (0.125, 0.6 and 1.7% NaCl solutions) were used and the tests were carried out using both male and female, water-deprived rats. When the rats were allowed the choice between a highly-preferred 0.125% NaCl solution and water, sulpiride (30 mg kg-1, i.p.) produced an increase in the intake of the two fluids. When naloxone (1 mg kg-1, s.c.) was given alone, it had no effect in this test of salt preference, but when given in combination, completely eliminated the hyperdipsic effect of sulpiride, providing behavioural evidence of a significant interaction between sulpiride and naloxone. When choices of either 0.6 or 1.7% NaCl solutions and water were given, the baseline levels of the consumption of the fluids were increased. Under these circumstances, sulpiride did not significantly increase the consumption of fluids; instead, naloxone significantly reduced the level of fluid consumption. In a further experiment, apomorphine, at dose levels which stimulate dopamine autoreceptors, had no effect on either fluid intake or saline preference in water-deprived male rats. Biochemical data showing that dopamine inhibits the release of beta-endorphin in the hypothalamus through the dopamine D-2 receptor, suggests a possible mechanism for a blockade of sulpiride-induced hyperdipsia by naloxone.

Animals↗

PubMed1985

Benzodiazepine receptor ligands and the consumption of a highly palatable diet in non-deprived male rats.

Non-deprived rats were familiarized with a highly palatable diet until baseline consumption in a 60-min daily access period had stabilised. The benzodiazepine receptor agonist midazolam (1.25-10.0 mg/kg, IP) produced a large, dose-related increase in food consumption during the first 30 min of access. It also produced significant, short-term hyperphagia in animals which had been partially pre-satiated on the diet before drug administration, an effect which was reversible by the benzodiazepine receptor antagonist Ro15-1788. Administered alone, Ro15-1788 (1.25-10.0 mg/kg, IP) had no intrinsic activity in the food consumption test. In contrast, CGS 8216 (2.5-40.0 mg/kg, IP) produced a marked dose-related suppression of food intake. This anorectic effect was shared by two benzodiazepine receptor inverse agonists, FG 7142 and DMCM, which also produced dose-dependent reductions in consumption. The effects on feeding produced by FG 7142 (20 mg/kg, IP) and DMCM (1.25 mg/kg, IP) were reversed by either Ro15-1788 (2.5 and 5.0 mg/kg) or midazolam (5.0 and 10.0 mg/kg). A matched anorectic effect produced by CGS 8216 (40 mg/kg) was not, however, reversed by either Ro15-1788 or midazolam. This suggests that at a high dose CGS 8216 may act by a mechanism different from that of the two inverse agonists. The feeding test described in the report proved sensitive to both hyperphagic and anorectic effects of drugs active at benzodiazepine receptors, pointing to a possible bi-directional control of palatable food consumption.

Animals↗

PubMed1985

Clonazepam-induced hyperphagia in nondeprived rats: tests of pharmacological specificity with Ro5-4864, Ro5-3663, Ro15-1788 and CGS 9896.

Nondeprived male rats were familiarised with daily 60 min access to a highly palatable diet, consisting of powdered rat diet, sweetened condensed milk and water. Clonazepam (0.625-5.0 mg/kg, IP) produced a substantial increase in food consumption within the first 30 min of access. The increase was similar across all dose conditions, suggesting that a maximal effect may have been achieved with a dose as small as 0.625 mg/kg. The hyperphagia induced by clonazepam was reversed by the benzodiazepine receptor antagonist, Ro15-1788 (5.0-20.0 mg/kg), indicating that the effect was benzodiazepine receptor-mediated. Treatments with the peripheral-type benzodiazepine agonist, Ro5-4864, did not induce a hyperphagic response. Instead, food consumption was significantly depressed following the administration of Ro5-4864 at 20 and 40 mg/kg, IP. A comparison of the clonazepam and Ro5-4864 data suggests that benzodiazepine-induced hyperphagia is mediated by central-type benzodiazepine binding sites. The pyrazoloquinoline, CGS 9896, binds with high affinity to benzodiazepine sites and has recently been described as a nonsedating anxiolytic. CGS 9896 (2.5-20.0 mg/kg, administered either IP or PO) did not affect consumption of the highly palatable diet. In consequence, anxiolytic and hyperphagic effects of drug actions at benzodiazepine receptors may be dissociated in the case of this compound. The atypical 1,4-benzodiazepine, Ro5-3663, a GABA antagonist which may act at the picrotoxinin site, produced a dose-related reduction in food consumption. Comparison with the results for Ro5-4864 rules out an interpretation for the anorexia in terms of anxiogenic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Analysis of dopamine D1 and D2 receptor involvement in d- and l-amphetamine-induced anorexia in rats.

The concept of dopamine receptor subtypes and the recent development of selective dopamine receptor agonists and antagonists raises the possibility of specific subtype involvement in amphetamine-induced anorexia, and, furthermore, provides the means to evaluate the possibility. Using a test of palatable food consumption by nondeprived male rats, our data confirmed a more potent suppressant effect of d-amphetamine on food intake, compared to l-amphetamine (potency ratio 5.32:1). The test proved sensitive, with ED50s of 0.28 mg/kg and 1.49 mg/kg for d- and l-amphetamine, respectively. The modest anorectic effect of 0.3 mg/kg d-amphetamine was completely reversed by the selective dopamine D1 receptor antagonist, SCH 23390, but was not affected by the selective D2 receptor antagonist, sulpiride. A matched feeding-suppressant effect of 1.0 mg/kg l-amphetamine was reversed at one dose of SCH 23390, but was unaffected by sulpiride. Stronger anorectic effects produced by 1.0 mg/kg d-amphetamine and 3.0 mg/kg l-amphetamine were not antagonized either by SCH 23390 or sulpiride. The selective D1 receptor agonist, SKF 38393, produced a dose-dependent reduction in food consumption, without producing behavioural stereotypy. Unlike amphetamine, SKF 38393 is not self-administered, and therefore may provide an example of a novel pharmacological dissociation between anorectic and reinforcing effects of drug treatments mediated by dopamine receptors. Our data implicate dopamine D1 receptors in the control of feeding responses, and suggest that these receptors may mediate the anorectic effect of small-dose amphetamine treatments.

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

PubMed1984

Naloxone suppresses fluid consumption in tests of choice between sodium chloride solutions and water in male and female water-deprived rats.

The effects of naloxone on fluid consumption by water-deprived rats trained to choose between a saline solution and water in a 15-min drinking test were examined. Rats of each sex were allocated to three groups and given access to 0.125% NaCl, 0.6% NaCl, and 1.7% NaCl, respectively, as the alternative to water. Under control conditions they drank substantially more of the hypotonic salt solutions than water, but drank slightly more water than hypertonic salt solution. Naloxone generally reduced fluid consumption, dose-dependently (0.01-10 mg/kg). In the cases of the two hypotonic solutions, the suppressant effect of naloxone was limited to saline solution. The usually low levels of water consumption were unaffected. In the case of the hypertonic solution, naloxone suppressed salt and water intakes by equivalent amounts. The effects of naloxone in the tests with the two higher salt concentrations depended upon sex. There was on example of a significant naloxone-induced reduction in saline preference (females; 0.125% NaCl v H2O). In other instances, saline preferences were not significantly modified. The results are briefly discussed in relation to current suggestions that naloxone may affect fluid consumption in ways which are taste-dependent (e.g., taste sensitivity, palatability, reward). An alternative view is also considered, that the effects of naloxone may be taste-independent, at least in the particular case of drinking in a two-choice test with saline and water.

Animals↗

PubMed1980

Protein, glycoprotein and glycolipid profiles of human arterial and venous tissues.

Selected normal human arteries and veins were solubilized with detergents, neutral salt buffers and organic solvents. Comparative sodium dodecyl sulphate polyacrylamide gels and thin layer chromatographic plates were developed and the patterns compared. The low molecular weight periodic acid--Schiff positive band seen in crude detergent extracts of vascular tissue is predominantly glycolipid. Arterial and venous tissues closely resemble one another with only minor differences in the glycoprotein and glycolipid patterns.

Arteries↗