Effect of prenatal heat stress on brain growth and serial discrimination reversal learning in the guinea pig

Exposure of pregnant guinea pigs to an environmental temperature of 42°C for 1 hr daily on Days 20–24 of gestation resulted in a significant reduction in the birthweight and brainweight of newborn offspring. These deficits persisted to early maturity and were still evident at 250 days of age following behavioral testing. Although some degree of postnatal neurogenesis and brain growth had occurred, this was not sufficient to compensate for the retarding influence of prenatal hyperthermia. Heat stress was also observed to seriously impair learning performance on the original discrimination task and this tendency persisted over the subsequent 4 reversals for both initial and perseverative errors. Impaired learning performance was related to reduction in brainweight. Animals with lower brainweights made significantly more initial, perseverative and total number of errors over the 5 problems. In addition, 12 of the 14 behaviorally tested stressed progeny had brainweights that were at least 2 standard deviations below the mean of the controls and as a result were classified as micrencephalic. Although heat stressed animals showed a significant reduction in the number of amacrine synapses in the inner plexiform layer of the retina, performance differences were not attributed to changes in synaptic organisation of the retinal circuitry or to visual or other ophthalmic defects, but brain function. Animals with higher mean maternal poststressing core temperatures gave birth to progeny which had smaller whole and part wet-brainweights. Examination of the effect of poststressing core temperature on brainweight revealed that brain growth, independent of bodyweight, was retarded when this temperature elevated above 41.5°C. This represented a rise of approximately 2.1°C above normal and for each 1°C rise above this temperature, brainweight was reduced by 0.4227 g of the control value. Analysis of the atmospheric content of the incubator during stressing sessions ruled out the possibility that changes in level of oxygen and carbon dioxide may have contributed to the retarding influence on fetal development and learning ability in the guinea pig.     

Transplacental kanamycin ototoxicity in the guinea pig

Summary The effect of kanamycin on the cochlear sensory epithelium of albino guinea pig fetuses was studied histologically following the administration of 200 or 400 mg/kg body weight kanamycin sulfate to the pregnant mothers for 8 consecutive days at different stages of gestation. Surface view analysis of Corti's organ revealed slight damage following treatment in the middle trimester of gestation and marked damage due to treatment in the last trimester. The pattern of hair cell loss induced during and after the functional differentiation of the cochlea resembled the pattern of ototoxic lesions in the adult ear. The assumed mechanisms for induction of teratogenesis by kanamycin in the fetal organ of Corti are discussed.Established investigator of the Chief Scientist's Bureau, Ministry of Health, Israel     

Ultrastructure of squamous epithelium during wound healing in palatal mucosa of guinea pigs

The ultrastructure of the epithelium of wounded guinea pig palate was studied. Twenty-four biopsies (animals) were used. Biopsies were taken 18, 48, 96, and 120 h after wounding. Essential changes in epithelial cell structure in response to wounding were as follows: microfilaments, suggested to represent actin-containing filaments, became evident in the cortical cytoplasmic zone. Micro tubules prevailed in the peripheral cytoplasm. Tonofilament bundles assumed the character of short tufts or delicate bundles and. the amount of non-bundled tonofilaments was increased. These observations suggest changes in the cytoskeletal/contractile system facilitating cell motility. The structure of lysosomal profiles indicates an enhanced phagocytic capability. Influence of fixation on preservation of non-membrane-bound organelles is suggested based on comparable morphometric data.     

Neuroleptic Blockade of the Effect of Various Neurotransmitter Substances

Abstract The antagonistic effect of neuroleptics to acetylcholine, histamine, 5-HT, and noradrenaline was examined in various in vivo and in vitro models. Piflutixol, a new potent thioxanthene neuroleptic, markedly antagonizes the effect of dopamine, noradrenaline, 5-HT and to some extent histamine, whereas the affinity for muscarinic receptors was rather weak. Clozapine and chlorprothixene on the other hand, have high affinity for muscarinic receptors and also antagonize the effect of histamine and 5-HT, whereas clozapine was a weak antagonist of noradrenaline and dopamine when compared to the effect of piflutixol. Chlorprothixene, however, also exhibits a rather good antagonism of noradrenaline and dopamine. Haloperidol proved to be weak in all models when compared with the other neuroleptics examined. Flupenthixol specifically antagonizes dopamine and noradrenaline, whereas fluphenazine was a more potent antagonist of dopamine than of the other transmitters. The data show, that neuroleptic compounds possess very different profiles with regard to interaction with various neurotransmitter substances. It is suggested, that the rather potent anti 5-HT and antihistamine effects observed for certain substances may contribute to the central effect of these drugs.     

Inhibitory effect of 8-methoxysporalen plus UVA (PUVA) on the systemic induction of contact sensitivity to dinitrochlorbenzene (DNCB) in guinea pigs

Summary To investigate the influence of 8-MOP and UVA on the induction of cell-mediated immunity, guinea pigs, sensitized with a single injection of dinitrofluorbenzene (DNFB) in Freund's complete adjuvant (FCA) in all footpads and the nuchal skin, were treated with 8-MOP, UVA, or 8-MOP+ UVA on days 0, 2, and 5 and tested with dinitrochlorbenzene (DNCB) on day 14 after sensitization. Two control groups, exposed in a covered condition to the PUVA 4000 lamp, to observe the heat effect, showed a slightly enhanced contact sensitivity in comparison to the only sensitized control group. No altered reactivity was observed after irradiation with longwave UV light alone, whereas a statistically significant enhanced resp. reduced contact sensitivity was obtained after the treatment with 8-MOP alone and the combined action of 8-MOP +UVA, respectively.Dedicated to Prof. Dr. P. Laugier, Chairman of the Department of Dermatology, University of Geneva, Switzerland, on the occasion of his 70th anniversary     

In vitro profile of some opioid pentapeptide analogues

The opiate agonist potency of thirteen synthetic enkephalin pentapeptides has been examined on the electrically stimulated guinea pig ileum and mouse vas deferens preparations in comparison with methionine and leucine enkephalins, beta-endorphin and normorphine. Their antagonism by naloxone (Ke) was also assessed on each preparation. Our findings are compatible with, and are discussed in the context of, the hypothesis that these preparations possess at least two populations of receptors.     

Effects of morphine and naloxone on separation distress and approach attachment: Evidence for opiate mediation of social affect

In order to determine the relationship between endorphins and social attachment, the effects of morphine (an opiate agonist) and naloxone (an opiate antagonist) on various indices of attachment in guinea pigs were studied. In infants, crying or separation-induced distress vocalizations were significantly decreased by single injections of low morphine doses (0.25, .050 and 0.75 mg/kg) in a dose-dependent manner. Naloxone (1 mg/kg) reliably increased separation distress vocalizations in both juvenile and adult guinea pigs. Therefore, similar to opiate withdrawal symptoms, separation distress appeared to be alleviated by morphine and potentiated by naloxone. As for approach attachment, offspring/maternal proximity-maintenance time was significantly decreased by morphine (1.0, 2.5 and 5.0 mg/kg), suggesting that opiates may be capable of replacing a function normally subserved by endorphins in reinforcing attachments. These data support the hypothesis that an endorphin-based addiction-like process may underlie the maintenance of social attachments, and that separation distress may reflect a state of endogenous “endorphin withdrawal”.     

Efferents of the medial preoptic area in the guinea pig: An autoradiographic study

Medial preoptic axons were traced into the diagonal band of Broca and septum, particularly lateral septum. Other labeled fibers could be followed dorsally from medial preoptic area injections adjacent to the stria medullaris, and in the periventricular fiber system and the stria terminalis and its bed nucleus. The anterior and medial amygdaloid nuclei were labeled by fibers via the stria terminalis and others arching over the optic tract and through the substantia innominata. The lateral habenula was labeled. Labeled periventricular fibers reached the periventricular nucleus of the thalamus. Descending efferents were traced principally below the fornix and in the adjacent lateral hypothalamus to label the anterior hypothalamus, the tuberal nuclei, and median eminence. Axons of the medial preoptic area joined the medial part of the medial forebrain bundle and distributed to the reticular formation and the central gray of the midbrain and pons. A small amount of contralateral connections were described.     

[H]Doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates

[³H]Doxepin, a tricyclic antidepressant, binds to brain homogenates with two saturable components. The high affinity component, with a dissociation constant (K_D) of 0.26 nM, is associated with histamine H₁-receptors. This high affinity binding shows stereospecificity in that d-chlorpheniramine is 100 times more potent than the pharmacologically less active l-isomer. Its drug specificity and regional variation closely parallel those exhibited by [³H]mepyramine binding. The drug specificity of the low affinity component is distinct from that of histamine H₁-receptors, with no stereospecifityty for chlorpheniramine isomers. Furthermore, all the H₁-histamine antagonists tested display micromolar potency at the low-affinity doxepin sites but nanomolar potency at the high-affinity doxepin sites associated with a physiological histamine H₁-receptor. The drug specificity of the low affinity site does not correspond to that of any known neurotransmitter receptor. Tricyclic antidepressants display IC₅₀ values of 30–600 nM for the inhibition of [³H]doxepin binding to the low-affinity component with most values in the 0.1–0.3 μM affinity range.