Biomedical subjects

P Teitelbaum

Publications and source records attributed to P Teitelbaum.

At least 37 records · Page 2Linked to original sources

PubMed1989

Seemingly paradoxical jumping in cataleptic haloperidol-treated rats is triggered by postural instability.

Paradoxically, animals exhibiting haloperidol-induced cataleptic immobility can be induced to leap vigorously, by pushing them forward from behind. It is shown here that such jumping can also be produced by placing them on a board and tilting it tail-end upward until about 50 degrees above horizontal. In both situations, jumps only occurred when the animal's hindlegs began to slip forward, as they lost their postural stability. As alternatives to jumping from the slope, rats turned to face upwards (negative geotaxis), or adopted a spread-eagled posture during head-first downward sliding, with the body and head flattened against the substrate. All 3 responses to the sloping board were present in some undrugged rats. Such rats, and those given low doses of haloperidol (0.5, 1.0 mg/kg), were more likely to turn upwards than to jump or slide. At high doses (7.5, 10.0 mg/kg), they were more likely to slide downward than to turn or jump. Jumping was most likely to occur at an intermediate dose (5 mg/kg), approximately 60 min after injection. We suggest that in the absence of haloperidol, and at low doses, locomotion is dominant over reflexes defending static equilibrium, and hence rats are more likely to turn upwards (which involves stepping). In contrast, at higher doses, locomotion is more fully suppressed, reducing the likelihood of turning. At very high doses of haloperidol and later in the action of the drug, muscle tonus appears to be weakened, reducing the likelihood of jumping. This possibility was supported by the finding that combined injection of the optimal dose of haloperidol and 2 mg/kg diazepam reduced the ability to cling vertically (suggesting weakness of muscle tone). In such rats, jumping from the sloping board was decreased, and active downward sliding was increased. Thus, different factors influence the occurrence of jumping at different doses of haloperidol. However, these are all active defensive responses to postural instability, and hence are similar to the other reflexes used by haloperidol-treated rats to defend against displacement from static stable equilibrium, such as standing immobile, bracing, clinging, and righting. Jumping in response to loss of stability on the sloping board also occasionally occurred in undrugged rats. Unlike jumps by haloperidol-treated rats, those by undrugged animals only occurred when they could be directed to a safe landing place. Thus, if the board faced the edge of the table, so that the jump would carry the animal into space over the edge, undrugged rats either did not jump or jumped off the side of the board onto the table.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Recovery from axial apraxia in the lateral hypothalamic labyrinthectomized rat reveals three elements of contact-righting: cephalocaudal dominance, axial rotation, and distal limb action.

In earlier work, we showed that in rats, proprioceptive-tactile information is sufficient for contact-righting on the ground (from lying on one side to prone). Thus, axial rotation, starting with the shoulders and followed by the pelvis, occurs normally in labyrinthectomized animals with eyes occluded. After damage to the lateral hypothalamus, even with labyrinths intact, contact-righting is at first abolished (1-2 days postoperatively), and when it reappears, involves pushing by the hindlegs. Rostrocaudal contact-righting, involving axial rotation, takes 3-4 days to recover. If labyrinthectomy is combined with lateral hypothalamic damage, the deficit is exaggerated and recovery is greatly slowed down, now requiring 2-3 weeks. The present paper shows that during this prolonged period of recovery several transitional forms of righting are present, each produced by a different combination of limb and body axis movements. At first, axial rotation is absent, and righting is achieved only by pushing with the limbs. This is followed by a transitional form in which, even though axial rotation cannot be triggered directly by contact with the ground, it can be triggered indirectly as an allied reflex when the paw places on the ground. Eventually the body axis actively initiates the rotation to proneness (at first, in the pelvis, later in recovery, in the shoulders), with the limbs being carried. Recovery of axial rotation overlaps with the recovery of cephalic dominance, yielding complex intermediate forms of righting.

Animals↗

PubMed1989

Visual modulation of vestibularly-triggered air-righting in the rat.

Unlike cats, which can initiate righting in the air either with vestibular or visual input alone, the rat is dependent solely upon the labyrinths to trigger this response. We show, however, that the rat can modulate the onset and speed of its rotation according to the height above the ground from which it is dropped. In the absence of vision, rates initiate rotation with a latency of about 50 ms, irrespective of the height from which they are dropped. With vision, rats can modulate their latency to begin rotation, from about 102 ms at 50 cm, to about 39 ms at 7.5 cm. Similarly, as height of release decreases, the speed of rotation (i.e. degrees/ms) increases. Thus, in rats, even though vision cannot trigger air-righting, it does adaptively modulate this behavior as an allied reflex, increasing the likelihood that the animals will land on their feet.

Animals↗

PubMed1989

Metabolic fate of the new anti-ulcer drug enprostil in animals. 1st communication: absorption, distribution and excretion in the mouse, rat and rabbit.

Absorption, distribution and excretion of [3H]-enprostil ((+-)-11a,15a-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorpr osta -4,5,13(t)-trienoic acid methyl ester, TA-84135), a new anti-ulcer prostaglandin, were studied in mice, rats and rabbits. Radioactivity associated with enprostil was rapidly absorbed from the gastrointestinal tract with Tmax values of 15 or 30 min. Absorption was also efficient inasmuch as approximately 80% of an oral dose was recovered in bile and urine in 24 h in bile duct-cannulated rats. Experiments in pylorus-ligated, bile duct-cannulated rats demonstrated that enprostil was mainly absorbed from the intestine, rather than from the stomach. In mice given oral doses of 2, 8 and 32 micrograms/kg, Cmax and AUC values of enprostil radioequivalents increased proportionately to the increase in dose, indicating linear kinetics over this dose range. Distribution of enprostil-associated radioactivity was investigated in rats by quantitating tritium in various tissues after the oral administration of [3H]-enprostil. Radioactivity in tissues was highest at 15 or 30 min after dosing. Highest levels of radioactivity were found in the stomach and intestines, the organs which came into direct contact with the dose, and the liver and kidney, the organs involved in excretion of enprostil. The rate of elimination of enprostil-associated radioactivity from all tissues and from plasma was similar. Enprostil-associated radioactivity did not accumulate in any tissue. Radioactivity was found in fetuses following oral administration of [3H]-enprostil to rats on the 12th or 19th day of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

[125I]2-iodo-3,7,8-trichlorodibenzo-p-dioxin-binding species in mouse liver induced by agonists for the Ah receptor: characterization and identification.

The admininistration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to C57BL/6J mice produces a dose-related increase in the hepatic uptake of [125I]2-iodo-3,7,8-trichlorodibenzo-p-dioxin ([125I]Cl3DpD) in vivo and the binding of the radioligand to liver homogenate in vitro [Mol. Pharmacol. 36: 121-127 (1989)]. The TCDD-induced hepatic binding species was found to be predominantly in the microsomal fraction and was inactivated by heating at 60 degree, trypsin, and mercurials. The TCDD-induced binding species was found to have an apparent equilibrium dissociation constant, KD, ([125I]Cl3DpD) of 56 +/- 16 nM and a pool size, Bmax, of 22 +/- 5 nmol/g of liver. A number of halogenated dibenzo-p-dioxins, biphenyls, and polycyclic aromatic hydrocarbons compete with [125I]Cl3DpD binding to this species; all are aromatic and planar. The distinctive profile of this binding species, a protein of large pool size induced in the microsomal fraction of liver but not other tissues and induced by agonists for the Ah receptor, suggested that this moiety might be cytochrome P3-450. The coincidence of the major microsomal species covalently labeled with the photoaffinity ligand [125I]2-iodo-3-azido-7,8-dibromodibenzo-p-dioxin and that immunochemically stained with polyclonal antiserum that binds to cytochrome P3-450 confirms this hypothesis. This is a novel role for a cytochrome P-450 isozyme, as an induced sequestration site that enhances the hepatic localization of the agonist drug.

Animals↗

PubMed1989

Stimulation of in vivo hepatic uptake and in vitro hepatic binding of [125I]2-lodo-3,7,8-trichlorodibenzo-p-dioxin by the administration of agonist for the Ah receptor.

[125I]2-lodo-3,7,8-trichlorodibenzo-p-dioxin ([125I]Cl3DpD), a radiolabeled, isosteric, analogue of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was synthesized and used to study in vivo tissue localization and in vivo tissue binding. Twenty-four hours after the administration of a tracer dose (1 X 10(-10) mol/kg) of [125I] Cl3DpD to C57BL/6J mice, the hepatic concentration of radioactivity was 1-2% of the administered dose, whereas in mice pretreated with TCDD (1 X 10(-7) mol/kg), the hepatic accumulation of radiolabel was 25-30% of that administered. Liver homogenate from TCDD-treated mice bound 4 to 10 times more [125I]Cl3DpD than homogenate from control mice. The enhancement of in vivo uptake and in vitro tissue binding of [125I]Cl3DpD by TCDD administration was confined to liver and was not observed in other tissues examined, kidney, lung, spleen, small intestines, and muscle. The administration of TCDD to C57BL/6J mice produces dose-related stimulation of in vivo hepatic uptake of [125I]Cl3DpD, binding of radioligand to liver homogenate, and hepatic aryl hydrocarbon hydroxylase activity, with the dose for half-maximal stimulation, ED50, varying from 1.5 to 4.0 x 10(-9) mol/kg. In congenic C57BL/6J (Ahd/Ahd) mice, which express the lower affinity Ah receptor, the ED50 values for all three responses were shifted to approximately 10-fold higher doses. 3,3',4,4',5,5'-Hexabromobiphenyl, a weak agonist for the Ah receptor produced a dose-related stimulation of these three responses in C57BL/6J mice (ED50 values of approximately 5 X 10(-7) mol/kg), but was without effect in C57BL/6J (Ahd/Ahd) mice. Stimulation of vivo hepatic uptake and in vitro liver homogenate binding of [125I]Cl3DpD was produced by administration of Ah agonists, such as 2,3,7,8-tetrachlorodibenzofuran and beta-naphthoflavone, but inactive congeners and other compounds that do not act via the Ah receptor, e.g. phenobarbital and pregnenolone-16 alpha-carbonitrile, did not evoke these effects. Thus, TCDD and other Ah agonists act through the Ah receptor to increase a liver binding species that increases the hepatic uptake of [125I]Cl3DpD in vivo and binding of this radioligand to liver homogenate in vitro.

Animals↗

PubMed1988

Bioavailability of soil-bound TCDD: oral bioavailability in the rat.

The implications to the public health of trace amounts of 2,3,7,8-TCDD in the environment are under evaluation by regulatory agencies in the United States and Western Europe. One major consideration in such evaluations is the contribution to human exposure via ingestion of TCDD-contaminated soil. An 80% figure is under consideration by some regulators for estimated human exposure. A contractor for one agency has, in fact, used a value of 100% bioavailability for estimating human bioavailability. Several studies have investigated the oral bioavailability of TCDD from contaminated soil in animals. Most have reported estimates of 25-50%, although one has reported less than 0.5 and 85%, depending on the source of the contaminated soil. This paper reports an oral bioavailability of approximately 43% in the rat dosed with three environmentally contaminated soil samples from Times Beach, Missouri. This figure did not change significantly over a 500-fold dose range of 2 to 1450 ng TCDD/kg of body weight for soil contaminated with approximately 2, 30, or 600 ppb of TCDD. The relevance of animal oral bioavailability data for the human remains to be evaluated. However, since regulatory agencies use animal data for extrapolating to humans, the 43% or 25-50% figure would be more accurate than the 80 or 100% estimates.

Administration, Oral↗

PubMed1988

Bioavailability of soil-bound TCDD: dermal bioavailability in the rat.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an unwanted by-product formed during the manufacture of hexachlorophene and phenoxyherbicides, has been found as an environmental contaminant in many U.S. and Western European sites. This study examines in the rat the degree of dermal absorption of TCDD bound to soil. Such information would assist regulatory agencies in evaluating the degree of exposure of humans who come in contact with TCDD-contaminated soil. Several parameters which may influence dermal absorption were studied, including TCDD dose, duration of contact, presence of crankcase oil as a co-contaminant, and environmentally contaminated vs laboratory-prepared soil. The dermal penetration of TCDD following 4 hr of contact with skin was approximately 60% of that following 24 hr of contact (P less than or equal to 0.05). Following 24 hr of contact with the skin, the degree of dermal uptake of TCDD contaminated soil was approximately 1% of the administered dose. Under the conditions of the present study, the degree of uptake does not appear to be influenced to any significant extent by the concentration of TCDD on soil, the presence of crankcase oil as co-contaminants, or by environmentally vs laboratory-contaminated soil. Although a number of parameters examined in this study did not significantly influence the degree of dermal absorption of TCDD in the rat following 24 hr of contact with the contaminated soil, the unqualified use of the 1% value to estimate human exposure would overestimate human exposure, since there is general agreement among researchers that rat skin tends to be more permeable than human skin to highly lipid-soluble compounds such as TCDD.

Animals↗

PubMed1988

Escalation of feline predation along a gradient from avoidance through "play" to killing.

In this article, we show that feline predation involves a continuous gradient of activation between defense and attack and that predatory "play" results from an interaction of the two. Benzodiazepines (oxazepam, diazepam) escalated attack toward killing, so that cats that had avoided mice prior to the drug now played with them, cats that had originally played now killed, and cats that killed mice now did so with less preliminary contact. In such shifts, no sharp demarcation between play and predation was evident. Lateral hypothalamic lesions disrupted the escalation of attack. During recovery, attack was escalated once again along the gradient toward killing, but in the absence of both defense and play. A similar result was obtained in intact killers and nonkillers by the application of mild tail pinch. These results suggest that play with prey is a misnomer for predatory behavior that fails to escalate along the gradient between defense and attack. Movement notation analysis revealed that playful movements are adaptive in that they protect the cat from injury.

Aggression↗

PubMed1987

'Axial apraxia' in labyrinthectomized lateral hypothalamic-damaged rats.

Contact righting, that is, turning from a recumbent position to prone, is abolished for a few days after large electrolytic lesions of the lateral hypothalamus. With recovery, contact righting reappears, but does so in a distinct manner. At first the body is righted by backleg movements, in the absence of any active axial rotation. Later, righting switches from back to front, so that righting begins in the shoulders and then proceeds to the pelvis. Such righting is achieved by axial rotation, that is, the limbs are carried by the torso, rather than vice versa. Labyrinthectomy, when combined with lateral hypothalamic (LH) damage, slows this recovery (now taking as long as 3 weeks), and reveals many intermediate stages of contact-righting. The absence of axial rotation in the early stages of recovery from combined LH damage and labyrinthectomy is compared to the 'axial apraxia' seen in some parkinsonian patients.

Animals↗

PubMed1987

Pharmacological subtraction of the sensory controls over grasping in rats.

Catecholamine-depletion-induced catalepsy isolates and leaves intact an aggregate of allied reflexes (e.g., righting, standing still, bracing, and clinging) which involve all the body and limb segments in defending stable static equilibrium. Because other movement subsystems (locomotion, orienting, scanning, directed use of mouth or forepaws) are depressed, such animals cling in a vertical position for an abnormally long period of time. As a consequence, grasping reflexes may be studied independently of other responses. Haloperidol, a dopamine antagonist, abolishes visually elicited reaching and grasping, but leaves intact tactile and proprioceptive control of grasping. The grasping of haloperidol-treated rats can be further simplified by the pharmacological removal of the remaining sensory controls. The addition of morphine to haloperidol abolishes tactile grasping, while the addition of diazepam to haloperidol abolishes both tactile and proprioceptive (traction-elicited) grasping. Although visual, tactile, and proprioceptive grasping are abolished by haloperidol-plus-diazepam, some vestibular input to clinging remains: such rats, in response to being held vertically upright in the air, flex their digits with sufficient strength to allow them to cling vertically. The strength of forepaw digit flexion is severely diminished by labyrinthectomy, but the digits of the hindpaws appear to be unaffected. This residual non-labyrinthine digit gripping appears to be induced by proprioceptive inputs from the head, neck and torso in response to the vertical body position. Wrapping an elastic bandage snugly around the head and neck of a labyrinthectomized rat given haloperidol-plus-diazepam further diminishes the strength of forepaw digit flexion, and to a lesser degree hindpaw digit flexion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Abnormal gait sequence in locomotion after atropine treatment of catecholamine-deficient akinetic rats.

Excessive, abnormal locomotion occurs after a high dose (25-50 mg/kg) of atropine sulfate to rats already akinetic due to catecholamine deficiency from intraventricular administration of 6-hydroxydopamine. This abnormal locomotion involves an abnormal gait sequence [right (R) hindleg (H), left (L) foreleg (F), LH, RF] instead of the normal gait sequence (RH, RF, LH, LF). In such animals atropine progressively (i) decreases hindleg step size, (ii) decreases arching of the trunk, and (iii) increases foreleg step size. These factors combine to change the ratio of front/hind body support. If the body stretches too far and the hindleg step is too small, a given hindleg step supports insufficient weight to remove weight from the ipsilateral foreleg; consequently, the opposite foreleg must execute the next step, producing the abnormal gait sequence. Thus, atropine affects gait sequence indirectly; it acts on at least three variables that affect how body weight is distributed and shifted during locomotion. To maintain stability during such locomotion, gait sequence is appropriately altered.

Animals↗

PubMed1986

Bandage backfall: labyrinthine and non-labyrinthine components.

A cataleptic animal clings in a vertical position, unmoving, for abnormally long periods by supporting some of its weight on its hindlegs, grasping with the forepaws, flexing its forelimbs, and holding the head horizontal. When the head is snugly wrapped with a bandage, the head slowly falls backward, the neck hyperextends, the forelimbs extend and the grasp is released, resulting in the animal falling backward to the ground. It was earlier suggested that in cataleptic animals, the bandage inhibits vestibular and kinesthetic mechanisms of head support, yielding the backfall sequence [35]. However, preliminary experiments showed that labyrinthectomized rats made cataleptic by haloperidol fall backwards when placed in a vertical clinging position, even without a bandage, suggesting that in the rat the bandage-backfall reaction depends only on the vestibular system. In the present paper, this result is verified but, by additional experiments, the latter conclusion is shown to be incorrect. In labyrinthectomized rats made cataleptic by other means (lateral hypothalamic damage, or bulbocapnine), backfall from clinging did not occur unless a bandage was applied. Therefore, the bandage does indeed appear to inhibit the kinesthetic mechanisms that maintain head support in labyrinthectomized cataleptic rats. Haloperidol, particularly in high doses, greatly weakens postural support in labyrinthectomized rats (causing the animal to sag down and fall back when clinging), although the effect is not detectable in rats with labyrinths intact. However, labyrinthectomy reveals that the bandage can trigger an active dorsiflexion of the neck which in itself appears to inhibit clinging and righting. Bandage-induced dorsiflexion is present to a much lesser degree in intact animals, indicating that labyrinthine mechanisms inhibit the dorsiflexion reflex. Therefore, in the intact, cataleptic rat the bandage backfall reaction appears to be produced by the combined effects of a passive component (inhibition of kinesthetic support mechanisms), and an active component (elicitation of dorsiflexion of the neck).

Animals↗

PubMed1986

Morphine subtracts subcomponents of haloperidol-isolated postural support reflexes to reveal gradients of their integration.

Although cataleptic rats do not spontaneously orient, scan, or walk, they will cling, stand, right themselves in the air, and resist being displaced from a stable position (Schallert, Whishaw, De Ryck, & Teitelbaum, 1978). Morphine produces a state of immobility in which all reflexes used for stable static support (e.g., standing, righting, clinging, and bracing) appear to be inhibited (De Ryck, Schallert, & Teitelbaum, 1980). Addition of morphine to haloperidol abolished or reduced those reflexes used to defend against slow postural displacements (e.g., bracing) but left intact those used to protect against fast postural displacements (e.g., righting in the air). However, although intact, these responses to fast postural displacements were completely abolished by labyrinthectomy, showing that they were controlled only by vestibular inputs. During recovery from morphine's effects, the responses to slow postural displacements reemerged, revealing fractional subcomponents. Furthermore, the reorganization of the subcomponents proceeded along specific body gradients; for example, bracing and standing reemerged caudorostrally, while at the same time, righting and clinging reemerged rostrocaudally.

Animals↗

PubMed1985

Effects of pontine reticular formation lesions on optokinetic head nystagmus in rats.

Electrolytic lesions were produced in the pontine reticular formation (PRF) of adult hooded rats. Unilateral lesions abolished quick phases of optokinetic head nystagmus to the side of the lesion. Some lesions also had temporary effects on slow phases of optokinetic head nystagmus. Effects of bilateral lesions were similar, except that they affected head movements in both directions. A class of "fast" head movements abolished by PRF lesions thus emerges that is analogous to the class of rapid eye movements abolished by similar lesions in other species, a finding that can be related to the coupling which has been observed between "fast" head and eye movements.

Animals↗

PubMed1985

Vestibular versus tail-pinch activation in cats with lateral hypothalamic lesions.

Mild tail-pinch induces eating in animals which are aphagic following lateral hypothalamic lesions. This study compares the specificity of the behavior produced by tail-pinch to that produced by vestibular stimulation in cats which are akinetic and aphagic following lateral hypothalamic lesions. In these cats, tail-pinch elicited licking and biting at food while vestibular stimulation preferentially elicited forward locomotion. These results suggest that such stimuli activate specific movement subsystems rather than producing general, nonspecific arousal.

Animals↗

PubMed1985

Fractionation of the cataleptic bracing response in rats.

In haloperidol-treated rats, bracing, i.e., resistance to displacement along a horizontal surface, was found to involve four components: gripping by the digits, extension by the limbs, stiffening of the body axis and arching the vertebral column towards the displacing force. Labyrinthectomy weakened the bracing of the forequarters as did application of a head bandage. Labyrinthectomy, when combined with head bandage, completely abolished all forequarter bracing responses. Neither manipulation affected the bracing responses of the hindquarters. The hindquarter bracing reaction was abolished by application of an abdominal bandage, which left most of the forequarter responses intact. Isolation of fore- and hindquarter bracing responses revealed that whereas gripping by the digits and extension by the limbs could occur independently in either part of the body, stiffening of the body axis and arching of the vertebral column originated in the hindquarters. However, although these latter components of bracing originate in the hindquarters, as evidenced by their abolition with application of an abdominal bandage, their recruitment into the anterior of the body only occurred when the bracing of the forequarters was unimpaired. Either labyrinthectomy or head bandage prevented stiffening and arching of the vertebral column from occurring in the forequarters, even though these procedures had no effect on the hindquarters. Labyrinthectomy, head bandage and abdominal bandage all fractionated the bracing response over a wide range of haloperidol dosages (0.5, 1.0, 2,5, 5,0 and 7.5 mg/kg).

Animals↗

PubMed1985

Head displacement and bracing in haloperidol-treated rats compared to rats with lateral hypothalamic damage.

A characteristic of catecholamine-depletion-induced catalepsy is that such animals resist horizontal displacement, forward, backward or sideward, by bracing, i.e., pushing against the displacing force rather than stepping away as do normal animals. In this report the bracing responses of two cataleptic preparations were compared: (1) intact rats given haloperidol, a dopamine antagonist, and (2) rats with large lesions of the lateral hypothalamus (LH). Although both preparations exhibited exaggerated bracing responses when pushed, the LH rats acted in a non-cataleptic manner when pushed backward by the head; they retreated backward. The backward walking was a head-elicited response, because pushing the body backwards by the shoulders elicited bracing, not walking. Other forms of head displacement elicited body bracing if the body's stability was challenged: as when the head (and thus the body) was pulled forward; or no strong bracing responses if the head was displaced without affecting the body's stability, i.e., when as the head was pushed laterally. Therefore, retreating rather than bracing was elicited by one specific form of head displacement: backward. In contrast, haloperidol-treated rats braced whenever the body's stability was challenged, including when the head was pushed backward.

Animals↗