Prenatal exposure to methylazoxymethanol (MAM) acetate: effects on ultrasonic vocalization and locomotor activity in rat offspring.
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Biomedical subjects
Publications and source records attributed to V Cuomo.
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Early postnatal administration of SCH 23390 and sulpiride induced marked changes in the ultrasonic vocalization elicited by the removal of rat pups from their nest. In particular, SCH 23390 produced a significant increase in the length, as well as in the sound pressure level, of ultrasonic calls; moreover, a significant decrease in minimum and maximum frequency values was found in pups treated with this DA1-receptor antagonist. Sulpiride significantly reduced the rate of calling, as well as the pressure level of sounds, whereas it did not influence other parameters of the ultrasonic emission. These behavioural alterations seemed to be the consequence of an impaired functional maturation of the dopamine (DA) system; however, the different changes caused by SCH 23390 and sulpiride, respectively, suggest that DA1- and DA2-receptor populations could play a distinct role in the ultrasonic calling during early postnatal life.
Several experimental models for studying emotion and motivation in laboratory animals have been developed in these last years. A new interesting approach for evaluating some emotional and motivational states in rodents is represented by the measurement of ultrasonic emission in various situations, mainly: by infants when removed from the nest and apparently under stress, cold and/or hunger; during sexual behaviour; during aggressive encounters; in response to aversive stimuli. The calls differ somewhat in their physical characteristics depending on the species and on the situation. Examples of ultrasonic emissions which could be valuable as bioassays in Behavioural Toxicology are described here together with what is known of the biological function of the calls.
The effects of prolonged postnatal administration of haloperidol (H) on ultrasonic vocalization elicited by the removal of rat pups from their nest were investigated. The results show that the number of ultrasonic calls was significantly reduced by H exposure from the 8th until the 14th day after birth. Conversely, this neuroleptic significantly increased the duration of ultrasound from the 4th up to the 16th day of age. Moreover, changes in the frequency of calls were produced by early postnatal treatment with H. These alterations could be due to an impaired functional maturation of the dopaminergic system produced by neonatal exposure to H. Furthermore, the present data suggest that ultrasonic vocalization may be considered as an early sensitive indicator of subtle changes elicited by the postnatal treatment with a dopamine receptor blocking agent at dose levels below those associated with overt signs of neurotoxicity.
SCH 23390 (SCH), a DA1-receptor antagonist, did not influence the decrease in locomotor activity elicited by a dose of apomorphine (20 micrograms/kg) believed to stimulate DA autoreceptors in rats. Conversely, SCH antagonized the effects on locomotion and the stereotyped behaviour elicited by a dose of apomorphine (1 mg/kg) which stimulates postsynaptic DA receptors. These results showing that the behavioural effects produced by small and large doses of apomorphine are differently affected by SCH, further confirm that DA autoreceptors can be pharmacologically distinguished from postsynaptic DA receptors.
Spectinomycin displays a dose-dependent neuromuscular blocking activity in vivo. The neuromuscular blockade elicited by spectinomycin is potentiated by d-tubocurarine. Neostigmine methylsulfate is unable to reverse the neuromuscular blocking activity of spectinomycin, whereas calcium chloride counteracts the neuromuscular blockade induced by this antibiotic.
The Corollospora maritima, a marine ascomycete, has been used as an experimental model to investigate the possibility that age pigments can be considered indicators also of environmental stress. Synthetic sea water enriched with iron or copper has been inoculated in a broth culture of the fungus. After 5 days of incubation the mycetes were assayed for lipofuscin fluorescent pigment and malondialdehyde content. The presence in the culture medium of the heavy metal ions results in an increase of the lipofuscin and malondialdehyde production. The same evidence has been obtained with sea water samples collected at seven sites along the coast of the Gulf of Naples (Italy): the lipofuscin and malondialdehyde production increases proportionally with the copper and iron pollution in the sea water.
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A statistical analysis of the autocorrelation characteristics of active polypeptides has been carried out by means of the correlogram method. It is shown that the amino acid sequences of the analysed proteins, considered as a whole, are autocorrelated and that the correlograms characterize each protein reflecting its three-dimensional structure.
The decrease in the Bmax value of 3H-dihydroalprenolol (3H-DHA) binding to cortical membranes of rat brain induced by long-term administration of desipramine (DMI) was prevented by concomitant treatment with parachlorophenylalanine (pCPA). Acute administration of DMI significantly decreased locomotor activity in saline- and (pCPA)-pretreated rats. DMI-induced inhibition of locomotor activity was abolished in (pCPA)-pretreated rats chronically treated with DMI. Conversely, in pCPA-pretreated animals, acute DMI could still significantly decrease the locomotion of chronically DMI-treated rats. The data presented indicate that an intact serotoninergic system is required to enable antidepressant drugs to induce biochemical and behavioral changes following their chronic administration.
Chronic treatment with antidepressants has been shown to produce a subsensitivity of noradrenergic neurons, both at presynaptic and postsynaptic sites. Important mechanisms, whereby the activity of noradrenergic neurons is regulated, could be the sensitivity of presynaptic alpha 2-adrenoceptors and the participation of transynaptic mechanisms involving other neurons. In this report we demonstrate that transynaptic factors involving the serotonergic system may be relevant to the regulation of the function of alpha 2-receptors in antidepressant chronically treated animals. In fact, we provide evidence of a markedly deminished responsiveness of noradrenergic neurons to an alpha 2-agonist (clonidine) or antagonist (mianserin) in biochemical and behavioral studies following serotonergic denervation with 5,7-dihydroxytryptamine. These results indicate that a functional interrelationship between serotonergic and noradrenergic systems might play an important role in the adaptive changes which bring the noradrenergic neurons to a lower level of activity after chronic antidepressant administration.
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C57 BL/6J (C57) mice display a particular pattern of responses following morphine administration, such as a rapid development of tolerance to the pharmacological action of the opiate and an increase in locomotor activity after a single injection of the drug. We have measured met-enkephalin content and the responsiveness of different opiate receptors after repeated administration of morphine and naloxone. Prolonged morphine administration changes neither met-enkephalin levels, nor the density of the opiate receptors in mice brain. In contrast repeated administration of the opiate antagonist naloxone, produced a marked increase in the number of 3H- DHM and 3H- DADLE binding sites in striatum and brainstem without modifying met-enkephalin concentrations. Behavioral studies have indicated that the morphine-induced increase in locomotor activity is enhanced in naloxone pretreated mice, thus suggesting a possible correlation between the behavioral response to morphine in C57 mice and the higher number of opiate receptors in the striatum.
Prenatal administration of typical (desipramine, DMI) and atypical (viloxazine, VX and mianserin, MS) antidepressants, at dose levels which do not influence reproductive success or neonatal mortality, produces subtle behavioural changes in offspring of treated rats. Physical signs, such as pinna detachment (unfolding of external ear) and eye opening, were not modified by prenatal exposure to any of the antidepressants tested. However, at 23 days of age, DMI, MS and VX (only in males) pretreated rats showed higher levels of locomotor activity with respect to the control group. At 60 days of age, locomotor activity levels in DMI-exposed animals were still higher than in the saline-pretreated rats.
Two months after prolonged administration of estradiol (ES) in female rats the behavioural responsiveness to muscimol, a GABA receptor stimulating agent, and to apomorphine, a dopamine receptor agonist, was significantly altered. In particular, the decrease in locomotor activity induced by a challenge dose of muscimol (0.5-1 mg/kg) was significantly attenuated in ES-pretreated animals. Conversely, the intensity of stereotyped behaviour elicited by a challenge dose of apomorphine (1 mg/kg) was significantly increased in ES-pretreated rats. The behavioural alterations in the response to muscimol and apomorphine presumably result from the production of central GABA receptor subsensitivity and dopamine receptor supersensitivity respectively, induced by the prolonged ES administration.
A long term treatment with the delta-selective opiate antagonist NN-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154129) produces an increase in the number of delta-opiate binding sites, whereas the same treatment with the non selective opiate antagonist naloxone results in an enhancement of both mu- and delta-binding sites. This biochemical effect in naloxone-pretreated mice is paralleled by a more pronounced increase in locomotor activity induced by a challenge dose of morphine. In contrast, no difference in the effect of morphine was seen in ICI 154129-pretreated mice with respect to control. These data suggest that the locomotor response to morphine in C57 mice is not mediated through delta-opiate receptors.
O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1----6)-O-[2,6-diamino-2,3,4,6 -tetradeoxy-alpha-D-erythro-hexopyrano-hexopyranosyl-(1----4 ) ]-2-deoxy-L- streptamine (dibekacin), like other known aminoglycoside antibiotics, possesses a dose-dependent neuromuscular blocking activity in vivo. d-Tubocurarine, at a dose which per se does not influence the contraction of gastrocnemius muscle elicited by sciatic nerve stimulation, significantly potentiates the neuromuscular blockade produced by dibekacin. Neostigmine methylsulfate is unable to reverse the neuromuscular blocking activity of dibekacin, whereas calcium chloride antagonizes the neuromuscular blockade produced by this antibiotic.
Acute administration of desipramine, mianserin and viloxazine produces a significant decrease of locomotor activity in rats. Conversely, the locomotion of rats receiving the antidepressants for a prolonged period of time is not modified with respect to control animals. Moreover, the reserpine-induced decrement of locomotion is not influenced by chronic treatment with any of the antidepressants used in the present study. Since tolerance develops rapidly to these behavioural effects they may be indicative of compensatory changes in neuronal systems which may occur during prolonged antidepressant treatment.