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J Orbach

Publications and source records attributed to J Orbach.

At least 19 recordsLinked to original sources
PubMed1998

Cholinergic/serotonergic interactions in hypothermia: implications for rat models of depression.

This article reviews published reports and presents new evidence that support a number of commonalties between lines of rats selectively bred for differences in cholinergic (muscarinic) and serotonergic (5-HT1A) sensitivity. The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression derived for cholinergic supersensitivity, is more sensitive to both cholinergic and serotonergic agonists, and exhibits exaggerated immobility in the forced swim test relative to the control, Flinders Resistant Line (FRL), rat. Similar exaggerated responses are seen in a line of rats recently selected for increased sensitivity to the 5-HT1A agonist, 8-OH-DPAT (High DPAT Sensitive--HDS), relative to lines selectively bred for either low (Low DPAT Sensitive--LDS) or random (Random DPAT Sensitive--RDS) sensitivity to 8-OH-DPAT. For both the FSL and HDS rats, their exaggerated immobility in the forced swim test is reduced following chronic treatment with antidepressants. The present studies examined further the interaction between cholinergic and serotonergic systems in the above lines. Supersensitive hypothermic responses to 8-OH-DPAT were observed very early (postnatal day 18) in FSL rats, suggesting that both muscarinic and serotonergic supersensitivity are inherent characteristics of these rats. Scopolamine, a muscarinic antagonist, completely blocked the hypothermic effects of the muscarinic agonist oxotremorine in FSL and FRL rats, but had no effect on the hypothermic responses to 8-OH-DPAT, suggesting an independence of muscarinic and 5-HT1A systems. On the other hand, genetic selection of genetically heterogeneous rats for differential hypothermic responses to the muscarinic agonist oxotremorine were accompanied by differential hypothermic responses to 8-OH-DPAT, suggesting an interaction between muscarinic and 5-HT1A systems. Overall, these studies argue for an inherent interaction between muscarinic and 5-HT1A systems, which probably occurs beyond the postsynaptic receptors, possibly at the level of G proteins.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Lack of anxiety in an animal model of depression with cholinergic supersensitivity.

It has been suggested that anxiety and depression are correlated dimensions of behaviour. Consequently, this study investigated the behaviour of the Flinders Sensitive Line, an animal model of depression with cholinergic supersensitivity, in the elevated (+)-maze test of anxiety. The results indicate that anxiety responses (% open/total arm entries) do not differ between the Flinders Sensitive and Flinders Resistant (control) lines of rat (FSL vs. FRL, respectively). Treatment with 1.0 mg/kg of diazepam significantly increased % open/total scores to a similar degree in both lines, further suggesting that the lines do not differ in anxiety. It is concluded that the FSL rat is an animal model of depression without evidence for inherent alteration in anxiety-related behaviour.

Animals↗
PubMed1991

Early development of muscarinic supersensitivity in a genetic animal model of depression.

Adult Flinders-Sensitive Line (FSL) rats are significantly more sensitive to the behavioral and physiologic effects of muscarinic agonists than are control, Flinders-Resistant Line (FRL) rats; therefore, they resemble humans with depressive disorders. The present study examined the sensitivity of prepubertal and pubertal FSL and FRL rats to the hypothermic and locomotor inhibitory effects of the muscarinic agonist, oxotremorine, and compared these findings to the regional development of muscarinic receptor binding in similarly aged rats. The FSL rats were significantly more sensitive (-1.85 degrees +/- 0.2 degrees C) than the FRL rats (-0.65 degrees +/- 0.15 degrees C) to the hypothermic effect of 0.25 mumol/kg of oxotremorine at the earliest age tested (18 days postpartum) and became progressively more sensitive throughout the period of testing (FSL -2.8 degrees +/- 0.24 degrees C versus FRL -0.5 degrees +/- 0.16 degrees C at 61 days postpartum, data represent the mean +/- SEM of pooled male and female). Significant increases in muscarinic receptor number in FSL rat brain were observed only in older (61 days postpartum) rats. These results are consistent with the suggestion that the FSL rat is a genetic animal model of depression, but also indicate that the differences in muscarinic sensitivity cannot be accounted for exclusively by differences in the number, per se, of muscarinic receptors.

Aging↗
PubMed1982

Disruption of passive avoidance memory by REM sleep deprivation: methodological and pharmacological considerations.

The present experiments were designed to examine more closely the variables responsible for the disruption of passive avoidance memory produced by REM sleep deprivation. In the pharmacological study it was found that imipramine could reverse the memory disruption exhibited by rats maintained on large platforms (presumably not REM-deprived) while both imipramine and physostigmine were required to reverse the memory disruption exhibited by rats maintained on small platforms. In the methodological study it was found that those animals maintained on the smallest platforms and therefore having the largest weight to area ratio exhibited the greatest degree of memory disruption. It is concluded that further modification and verification of the platform techniques of REM deprivation is required before firm conclusions about its neurochemical basis and behavioural functions can be made.

Animals↗
PubMed1982

Cardiovascular function during treadmill exercise in the turkey.

1. Heart rate, arterial pressure and blood lactate levels were measured in turkeys over a range of running speeds on a treadmill. 2. Heart rates showed a hyperbolic increase with speed to a level approximately twice that recorded at rest. Arterial pressures were found to be lower than those previously reported for the turkey. During severe exercise, the mean value increased 37% above the resting level. 3. Blood lactate levels were greater at increased work loads, but after an initial rise, the levels remained steady during locomotion. 4. At rest, heart rate increased about 46% following parasympathetic blockade and decreased 19% with sympathetic blockade. During locomotion, parasympathetic tone is minimal. 5. In turkeys free of parasympathetic and beta-adrenergic influences, heart rate still increased at the highest running speed. Neither lactate nor ionotrophic effects appear to cause this increase.

Animals↗
PubMed1980

gamma-Aminobutyric acid stimulates intrinsic inhibitory and excitatory nerves in the guinea-pig intestine.

The sites of action of gamma-aminobutyric acid (GABA) were examined in preparations of the distal colon and ileum of guinea pigs. GABA caused transient relaxations of the longitudinal and circular muscle of the colon and transient contractions followed by relaxation of the muscle of the ileum. The responses of both parts of the intestine were antagonized by tetrodotoxin and by bicuculline. Nerve-free preparations of the longitudinal muscle of the ileum were not affected by GABA, even in concentrations up to 10(-4) g/ml. There was a marked tachyphylaxis of the responses to GABA. Relaxations in response to GABA were not affected by pentolinium or by a combination of phentolamine and propranolol. Contractions in response to GABA were blocked by hyoscine. Neither the ascending excitatory or descending inhibitory components of the peristaltic reflex in the distal colon were affected by bicuculline or by making the intestine tachyphylactic to GABA. The results indicate that GABA stimulates receptors mediating excitation of cholinergic excitatory and enteric inhibitory neurons whereas it has little or no direct effect on the muscle of the ileum or distal colon.

Amino Acids↗
PubMed1975

Effect of osmotic pressure on spontaneous afferent discharge in the nerves of the perfused rabbit liver.

Rabbit livers were perfused with Krebs solution via the portal vein and small bundles of the hepatic nerve were monitored for spontaneous afferent impulses arising in the liver. The concentration of the Krebs solution was varied by altering the amount of water in which the salts were dissolved. An alteration from 5% more concentrated to 5% more dilute and vice versa did not affect this spontantous discharge. Addition to the Krebs solution of up to 60 mM sucrose, of up to 22 mM mannitol or of 0.8 mM polyethylenglycol 6000 mol. wt. did not alter the frequency of impulses. Perfusion with bovine serum, or Krebs solution containing approx. 0.6 mM polyvinylpyrrolidone, mol. wt. 44000, or dextran mol. wt. 110000 increased the frequency of discharge in some nerve bundles. An alteration of 0.06 mM in the concentration of dextran produced a significant change of frequency. It is concluded that spontaneous discharge in some afferent hepatic nerves is influenced by colloidal osmotic pressure but not by changes of ionic osmotic pressure. The nerves affected differ from 'sodium-sensitive' nerves and from the 'osmoreceptors' of Niijima.

Action Potentials↗
PubMed1973

A study of compounds which initiate and block nerve impulses in the perfused rabbit liver.

1. A technique for the perfusion of the rabbit liver with Krebs solution is described: the hepatic nerves were monitored for centripetal action potentials. Spontaneous afferent activity, and a good response to stimulating agents persisted for 7 h or longer.2. Action potentials were elicited by injections or infusions of acetylcholine, 5-hydroxytryptamine, bradykinin, phenyldiguanide, adrenaline and various other compounds. From comparison with experiments carried out in vivo by other authors, it would appear that most of the nerves stimulated were afferent.3. Inhibition of action potentials, either those occurring spontaneously or those elicited by injections, was produced by aspirin, paracetamol, mepyramine, chlorpheniramine, procaine and lignocaine but not by morphine or atropine. Pentolinium produced some inhibition, as did hexamethonium in concentrations of about 7.5 mug/ml.4. Three methods for using the preparation for the assessment of local anaesthetic action are described.5. Lobeline, potassium cyanide and 2,4-dinitrophenol stimulated nerve bundles which were not stimulated by anoxia or hypoxia.

Acetylcholine↗
PubMed1972

A sympathetic reflex elicited by distension of the mesenteric venous bed.

1. The proximal ends of the distal portions of severed nerves coming from the small intestine were monitored for nerve impulses. When the mesenteric venous pressure was increased by mechanical obstruction of the portal vein there was a proportional increase in the frequency of afferent action potentials, the frequency falling immediately the venous pressure was reduced. The stimulus for the increased rate of nerve discharge appeared to be pressure within the mesenteric venous bed and not anoxia, for obstruction of the arterial supply to the gastrointestinal tract did not activate the same fibres.2. Obstruction of the portal vein led to an increased efferent nervous discharge to the intestines. The reflex increase persisted after bilateral vagotomy, after transection of the spinal cord at the level of C7 and after section of the hepatic nerves, but was abolished by section of the intestinal nerves.3. It is suggested that the spinal reflex is concerned with local distribution of blood and that the mesenteric venous ;volume' or ;stretch' receptors which initiate the reflex are similar to those described elsewhere in the body.

Action Potentials↗