Serotonin involvement in a motor disorder of Scottish terrier dogs

The effect of altering the concentration of 5-HT or the catecholamines upon an inherited neurological condition of Scottish terrier dogs which is characterized by episodes of muscular hypertonicity was assessed in a blind study. Alpha-methyl-paratyrosine and imipramine did not modify the condition. Amphetamine sulfate induced episodes; however, the episode was generally of shorter duration than the behavioral effect. The severity of the clinical rating was markedly increased by p-CPA. This increased severity was reduced by 5-HTP administration. The peripheral serotonin antagonist xylamidine tosylate did not alter the severity of the disease. Nialamide and 5-HTP had a significant beneficial effect. The increase in severity of the disease which follows a decrease in 5-HT coupled with a decrease in severity with an increase in 5-HT suggest certain serotoninergic neurons are involved in modulation of skeletal muscle tone.     

The motor disorder of classic Lesch-Nyhan disease

Reports describing the neurological features of Lesch-Nyhan disease (LND) vary widely, thereby implying the involvement of different neurological substrates. The movement abnormalities in 20 patients with LND were investigated. Dystonia was the most frequent and severe movement disorder. At rest, hypotonia was more frequent than hypertonia. These findings are compatible with basal ganglia dysfunction in LND.     

The relationship of callosal anatomy to paw preference in dogs

Previous studies have described the paw preference and asymmetry in dog brains, based on experimental studies. The purpose of the present study is to investigate a possible association between callosal anatomy and paw preference in dogs. The midsagittal area of the dog corpus callosum was measured in its entirety and in six subdivisions in a sample of 21 brains obtained from 9 male and 12 female mongrel dogs which had paw preference testing. The present study showed significant paw differences in dog corpus callosum. A posterior segment of the callosum, the isthmus, was significantly larger in the right pawedness than the left.     

Polymorphism of dental formula and segregation of its variants in a pedigree of kerry blue terrier dogs

Polymorphism of the dental formula was analyzed in a sophisticated pedigree of Kerry Blue Terrier. A lack of one or more lower premolars was observed in some dogs. Two different patterns of missing teeth were identified. One pattern consisted in agenesis of a second premolar, often in combination with agenesis of neighbor teeth, including the fourth premolar. In the second pattern, agenesis of a fourth premolar was expressed as an isolated abnormality. It was shown previously that the first pattern is inherited as a recessive trait with near complete penetrance. In this work, the control of a major-gene was demonstrated for the second pattern. This abnormality develops in 70-80% of mutant homozygotes and in no more than 20% of heterozygotes and wild-type homozygotes. It was shown that the two dentition abnormalities are controlled by different genes, which were designated LPA2 and LPA4 (Lower Premolar Agenesis).     

IgE responsiveness to Dermatophagoides farinae in West Highland white terrier dogs is associated with region on CFA35

Immunoglobulin E (IgE)-mediated hypersensitivity against environmental allergens, commonly including Dermatophagoides farinae, is associated with atopic diseases in both humans and dogs. We have recently identified a family of clinically healthy West Highland white terriers (WHWTs) with high-serum D. farinae-IgE levels. In this study, we investigated the genetic mechanism controlling IgE responsiveness in dogs by performing a genome-wide association study (GWAS) using the Affymetrix V2 Dog SNP array in 31 high-IgE and 24 low-IgE responder WHWTs. A gene-dropping simulation method, using SIB-PAIR software, showed significant allelic association between serum D. farinae-specific IgE levels and a 2.3-Mb area on CFA35 (best empirical P = 1 × 10(-5)). A nearby candidate gene, CD83, encodes a protein which has important immunological functions in antigen presentation and regulation of humoral immune responses. We sequenced this gene in 2 high-IgE responders and 2 low-IgE responders and identified an intronic polymorphic repeat sequence with a predicted functional effect, but the association was insufficient to explain the GWAS association signal in this population (P = 1 × 10(-3)). Further studies are necessary to investigate the significance of these findings for IgE responsiveness and atopic disease in the dog.     

The latent period of a conditioned motor reaction in dogs and cats]

A study was made of the temporal characteristics of motor reactions in cats and dogs to an instantaneous change in the shape of a photic signal. The latency value is an individual characteristic of the animal; it undergoes only slight fluctuations on different experimental days. No influence has been found of the intersignal interval magnitude (8--70 sec) on the duration of latencies. Longer experiment (about 300 signals in three hours) leads to longer latencies and their greater variability.     

Crayfish motor nerve terminal's response to serotonin examined by intracellular microelectrode

Measurements of resting potential and action potential in presynaptic branches of the excitatory motor axon to the crayfish opener muscle were made with intracellular microelectrodes during application of serotonin (10(-9)-10(-3) M). A 5-min exposure to 10(-6) M serotonin produced enhancement of excitatory junction potentials (EJPs) lasting about 1 h. The membrane potential of the presynaptic terminal was depolarized by about 5 mV; the depolarization subsided within 1/2 h. Concomitant reduction in amplitude of the presynaptic action potential, not accompanied by spike broadening, was observed. The presynaptic depolarization, and the enhancement of EJPs, were dependent on the presence of extracellular sodium but not extracellular calcium. A possible mechanism for serotonin's effect involves initial entry of sodium into the nerve terminal, with consequent increased availability of intracellular calcium. The subsequent long-lasting phase of EJP enhancement may result from an additional effect on the metabolism of the nerve terminal.     

D-LSD binding to brain homogenates: possible relationship to serotonin receptors

Using a rapid filtration technique we find stereospecific high-affinity $\text{d}$-LSD binding (4 × 10^?9M, half-saturation) in brain fractions from a number of subcortical as well as cortical brain regions. Among the putative neurotransmitters tested only serotonin effectively displaces $\text{d}$-LSD from this specific binding site. Moreover, only the serotonin-displaceable component of binding is saturable in a high-affinity range. No change is observed in specific $\text{d}$-LSD binding in forebrain homogenates from rats in which ascending serotonergic pathways are destroyed by lesions in the raphe nucleus. We conclude that a vast majority of the $\text{d}$-LSD binding sites may be associated with a postsynaptic serotonin receptor rather than a presynaptic receptor associated with serotonergic (raphe) inputs.     

Hallucinogens potentiate responses to serotonin and norepinephrine in the facial motor nucleus

The present investigation was designed to determine the effect of hallucinogens on the facilitating action of serotonin (5-HT) and norepinephrine (NE) in the facial nucleus. Intravenous administration of d-lysergic acid diethylamide (LSD, 5–10 μg/kg), mescaline (0.5–1.0 mg/kg), or psilocin (0.5–1.0 mg/kg) had no effect by themselves on the glutamate-induced excitation of facial motoneurons. In contrast, the facilitation of facial neuron excitation by iontophoretically applied 5-HT and NE was enhanced 6–10 fold by these hallucinogens. The LSD-enhanced responses to 5-HT and NE continued for at least 4 hours after administration of the hallucinogen. Iontophoretic application of LSD or mescaline (low currents) also markedly potentiated the facilitating effect of 5-HT and NE. Higher currents of LSD (15–40 nA) temporarily antagonized the response to 5-HT. The nonhallucinogen ergot derivatives lisuride and methysergide failed to potentiate the facilitating effects of 5-HT or NE. These observations suggest that hallucinogens potentiate the effect of monoamines on facial motoneurons by increasing the sensitivity of 5-HT and NE receptors. A novel mechanism regarding the psychedelic effects of hallucinogens is discussed.     

The psychophysiology of motor vehicle accident related posttraumatic stress disorder

Heart rate, BP, and electrodermal responses of four individuals with PTSD secondary to motor vehicle accidents (MVAs) were measured while they imagined two separate scenes related to their MVA. Results showed reliable HR responses to these images. In addition, SBP and DBP also showed some responsivity to the images while skin resistance level changed reliably in only 2 of 4 subjects. Psychophysiological measurement could play a role in the assessment and treatment of MVA-related PTSD.     

The relationship between Pseudo-nitzschia (Peragallo) and domoic acid in Scottish shellfish

The diatom genus Pseudo-nitzschia (Peragallo) associated with the production of domoic acid (DA), the toxin reposnsible for amnesic shellfish poisoning, is abundant in Scottish waters. A two year study examined the relationship between Pseudo-nitzschia cells in the water column and DA concentration in blue mussels (Mytilus edulis) at two sites, and king scallops (Pecten maximus) at one site. The rate of DA uptake and depuration differed greatly between the two species with M. edulis whole tissue accumulating and depurating 7 μg g⁻¹ (now expressed as mg kg⁻¹) per week. In contrast, it took 12 weeks for DA to depurate from P. maximus gonad tissue from a concentration of 68 μg g⁻¹ (now mg kg⁻¹) to <20 μg g⁻¹ (now mg kg^‐1). The DA depuration rate from P. maximus whole tissue was <5% per week during both years of the study. Correlations between the Pseudo-nitzschia cell densities and toxin concentrations were weak to moderate for M. edulis and weak for P. maximus. Seasonal diversity on a species level was observed within the Pseudo-nitzschia genus at both sites with more DA toxicity associated with summer/autumn Pseudo-nitzschia blooms when P. australis was observed in phytoplankton samples. This study reveals the marked difference in DA uptake and depuration in two shellfish species of commercial importance in Scotland. The use of these shellfish species to act as a proxy for DA in the environment still requires investigation.     

Electroencephalographic correlates of a pathologic inert motor reaction in dogs]

Changes in EEG were examined during setting in of a pathological inert motor reaction in dogs with parts of the tongue brought out and electrodes implanted in the motor cortical area and limbic structures. The reaction was formed when combining stimulation by a salt solution of the part of the tongue with electrical stimulation of the paw. The inert motor reaction is characterized by enhanced synchronization (theta-rhythm) in the hippocampus and increased amplitude of the beta-rhythm in the motor cortical areas. A frequency-amplitude analysis of the summary EEG has shown that the highest correlation was established at the beginning of elaboration of the inert motor reaction only between a small number of limbic structures (the hippocampus, the hypothalamus and the cingulate gyrus), then between all the examined structures of the brain; when the inert reaction became elaborated the number of structures with a high correlation coefficient diminished again and was reduced to the hippocampus, the hypothalamus and the cortical motor area.     

Electrophysiologic effects of serotonin on atrioventricular conduction in dogs

In 12 anaesthetized dogs acute effects of serotonin on the atrioventricular conduction system were studied by obtaining intracardiac electrograms. The significant increase in the heart rate and decrease in aortic pressure elicited by an intravenous infusion of 50 mg/kg.min serotonin for 30 minutes were comparable to those observed in previous investigations. Our data indicate a serotonin induced acceleration of the sinus node pacemaker and atrioventricular conduction by direct and indirect mechanisms.     

Neurotensin-induced colonic motor responses in dogs: a mediation by prostaglandins

The effects of systemic infusion of neurotensin (NT) were studied in four dogs fitted with strain-gauge transducers implanted on the ascending and descending colon. The motility index of the colon was enhanced for the duration of the 20 min NT infusion (20 pmol X kg-1 X min-1). Such stimulation was comparable to the colonic motor response elicited by feeding, i.e. the gastrocolic reflex. A period of hypomotility, lasting 40-90 min, occurred after either feeding or completion of NT infusion. Pretreatment with prostaglandin synthetase inhibitors, ketoprofene (KTP) and acetylsalicylic acid (ASA), reduced the magnitude of both the NT- and meal-induced hypermotility responses. The results suggest that the ability of NT to increase colonic motility may involve prostaglandin synthesis and that endogenous prostaglandin may exert a physiologic effect on colonic motor response to feeding. Moreover, these findings support a possible role for NT as one of the mediators involved in the non-neural mediation of the gastrocolic reflex.     

The blockade of serotonin uptake into synaptosomes:relationship to an interaction with monoamine oxidase inhibitors.

To test the hypothesis that the hyperpyrexia produced by meperidine and detromethorphan in rabbits pretreated with a monoamine oxidase inhibitor is related to inhibition of neuronal uptake of serotonin (5-hydroxytryptamine (5-HT)), fluoxetine (Lilly 110140) was studied. This potent and specific 5-HT neuronal uptake blocker was administered to phenelzine-pretreated rabbits and found to produce a lethal hyperpyrexia in doses equal to or greater than 2.5 mg/kg. The order of potency in blocking 5-[14C]HT uptake into synaptosomes prepared from rabbits was: fluoxetine greater than meperidine = dextromethorphan = levorphanol greater than anileridine greater than alphaprodine greater than morphine. Since fluoxetine, meperidine, and dextromethorphan produce hyperpyrexia in phenelzine-pretreated rabbits, whereas anileridine, alphaprodine, and morphine do not, there appears to be some correlation between the hyperpyrexic response and inhibition of 5-HT uptake. The exception is levorphanol, which is not hyperpyrexic despite being equipotent with meperidine and dextromethorphan in inhibiting 5-HT uptake. The ineffectiveness of levorphanol in producing hyperpyrexia may be due to its marked depressant properties, since the addition of another depressant drug (pentobarbital) antagonized the hyperpyrexic effect of meperidine.