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Biomedical subjects

V Cuomo

Publications and source records attributed to V Cuomo.

At least 73 records · Page 4Linked to original sources

Behavioral and neurochemical changes produced in rats by developmental treatments with psychotropic drugs.

The timing of developmental administration of psychotropic drugs affecting dopaminergic and GABAergic neurotransmission is crucial for the induction of specific neurobehavioral and neurochemical changes in rodents. Compensatory mechanisms occurring in response to a prolonged treatment with some neuroleptic and anxiolytic agents during development seem to be markedly different from those occurring in response to a prolonged administration in adult animals.

Animals↗

Ultrasonic vocalization as an indicator of emotional state during active avoidance learning in rats.

Adult male rats subjected to a two-way avoidance task emitted ultrasonic vocalizations (20-30 kHz) both during the presentation of the conditioned stimulus and the intertrial interval. The rate of ultrasonic calling decreased during the 75-trial session indicating that acquisition of the conditioned avoidance response (CAR) was inversely correlated with the rate of vocalization. The rate of acquisition of the CAR was most rapid in those rats that did not emit any vocalization during learning. These data suggest that ultrasonic calling during stressful situations may be sensitive indicator of underlying emotional states that interfere with the acquisition of a complex task.

Animals↗

Developmental aspects of neurobehavioural toxicity.

Previous work on the developmental aspects of neurobehavioural toxicity in rats and mice has shown the reliability of a variety of procedures aimed at assessing changes that may have widespread functional consequences, for example: (i) modified Fox batteries to study the maturation of various reflexes and responses after birth, (ii) activity/habituation and analgesia tests with age-specific profiles of reactivity to selected drug challenges, and (iii) simple learning tasks such as active and passive avoidance [1]. We will now summarize more recent work on other portions of the behavioural repertoire which deserve to be thoroughly assessed in "higher-tier" studies.

Aggression↗

Characterization of nucleotidic sequences using maximum entropy techniques.

A statistical method for characterizing nucleotidic sequences based on maximum entropy techniques is presented. The method uses only codon usage tables and takes into account the length of sequences, and preserves the information contained in each codon by a punctual index. We present the methodological aspects of the analysis, showing an application relative to nucleotidic sequences of eukaryotes.

Animals↗

Behavioural changes in the offspring of rats exposed to diazepam during gestation.

Primiparous pregnant Sprague-Dawley dams were administered a single daily s.c. injection of diazepam (0.1 and 1 mg/kg) or vehicle over gestation days 14-20. No differences in neonatal mortality and weight gain were found between the control and diazepam-exposed pups. Conversely, male pups prenatally treated with this benzodiazepine exhibited subtle behavioural alterations either during early postnatal life or during adulthood. In particular, a significant decrease in the locomotor activity of the diazepam-treated groups was found at the end of the second postnatal week (14-16 days). Furthermore, the administration of diazepam during gestation produced marked changes in the length of ultrasonic calls of rat pups removed from their nest. Finally, adult male rats (120 days of age) prenatally exposed to diazepam showed a notable impairment in copulatory activity as well as a significant decrease in the duration of ultrasonic (22 kHz) post-ejaculatory calls emitted during sexual behaviour. These findings suggest that late gestational exposure to diazepam induces both short- and long-term behavioural changes in rat offspring, changes characterized by altered activity patterns and emotional-motivational responsiveness to environmental challenges.

Animals↗

Liposome-delivered Si(IV)-naphthalocyanine as a photodynamic sensitiser for experimental tumours: pharmacokinetic and phototherapeutic studies.

The pharmacokinetic behaviour and phototherapeutic effectiveness of bis(di-isobutyloctadecylsil-oxy)-2,3-naphthalocyanatosilicon (iso-BOSiNc) incorporated into dipalmitoyl-phosphatidylcholine (DPPC) liposomes have been studied in Balb/c mice bearing an MS-2 fibrosarcoma. We found that iso-BOSiNc i.v.-injected at a dose of 0.5 mg kg-1 b.w. is preferentially transported by serum lipoproteins; in particular, the photosensitiser is associated with LDL (57.8% of total recovery in the serum) and HDL (35.7%) while minor amounts are associated to VLDL (2.63%) and other serum proteins (3.89%), Iso-BOSiNc concentrations greater than 1 microgram g-1 of tissue are recovered from the tumour at 12-48 h after administration while the ratio of iso-BOSiNc concentration in tumour and peritumoral tissue is greater than 10. Upon increasing the injected dose, the additional iso-BOSiNc is almost exclusively bound by HDL, which leads to large uptake of the photosensitiser by liver and spleen. The efficiency of iso-BOSiNc as a photodynamic agent was measured upon irradiation with a different dose-rate for a total light dose of 450 J cm-2. The extent of tumour necrotic area increases as a function of the time after the end of PDT treatment and reaches a maximum level after about 24 h. Moreover, the necrotic area is linearly dependent on the irradiation dose-rate up to 100 mW cm-2. In all there is substantial evidence that iso-BOSiNc delivered in a liposomal dispersion is a highly effective photosensitizer for PDT of tumours.

Animals↗

Neurobehavioral changes produced by developmental exposure to benzodiazepines.

The results reported in this review show that prenatal and/or postnatal administration of benzodiazepines, at dose levels below those associated with overt signs of neurotoxicity, produces both short- and long-term alterations in rats. Most of these behavioral changes are characterized by altered activity patterns and emotional/motivational responsiveness to environmental challenges.

Animals↗

A new experimental approach for detecting emotional and motivational changes produced by neuroactive compounds in rodents.

A new potential approach for detecting subtle changes of emotional and motivational states in rodents is represented by the analysis of ultrasonic vocalizations emitted in a variety of situations. The ultrasonic calls differ somewhat in their physical characteristics depending on the species and on the situation. The results of our studies on the effects of various neuroactive substances on ultrasonic emissions during neonatal life and during sexual behaviour are briefly described here together with what is known of the biological function of the calls.

Animals↗

Mediation of rat postejaculatory 22 kHz ultrasonic vocalization by dopamine D2 receptors.

We investigated the role of dopamine receptor subtypes in the regulation of ultrasonic vocalization and masculine copulatory behavior. Intact sexually experienced male Long-Evans rats were treated with saline, selective dopamine D1 (SKF 38393) and D2 (LY 171555) receptor agonists and with selective dopamine D1 (SCH 23390) and D2 (raclopride) receptor antagonists 15 and 30 min before the 30-min test session, respectively. Mating stimuli were ovariectomized female rats injected SC with estradiol benzoate (8 micrograms/0.1 ml/rat) and progesterone (200 micrograms/0.1 ml/rat), 48 and 4 hr before the test session, respectively. We found a decrease in the number of intromissions required to reach ejaculation in animals treated with SKF 38393 (10 mg/kg/IP), LY 171555 (doses ranging from 0.01 to 0.5 mg/kg/SC) and with raclopride (0.1 mg/kg/SC). LY 171555 reduced the postejaculatory vocalization (PEV) in a dose-dependent fashion with complete suppression at the highest dose. No other parameters of sexual behavior were affected by this treatment. Raclopride, a dopamine D2 receptor antagonist, antagonized the suppressive effects of the D2 agonist LY 171555 on the PEV (and also decreased the number of intromissions to reach ejaculation), whereas SCH 23390, a dopamine D1 receptor antagonist, did not. Raclopride, given alone at the dose of 0.5 mg/kg/SC, almost completely suppressed all behavioral activity, whereas the lower dose (0.1 mg/kg) decreased intromission frequency and increased the length of the 22 kHz PEV. Therefore, we suggest that 22 kHz PEV is under the control of dopamine D2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Subtle behavioural changes produced in rat pups by in utero exposure to haloperidol.

Prenatal exposure to a dopamine receptor blocking agent such as haloperidol (given to the mother at a dose of 0.5 mg/kg s.c. from day 4 to day 15 of gestation) produced subtle behavioural changes in rat pups. Haloperidol decreased the rate of ultrasonic vocalization in 4-day-old male pups removed from the nest. The changes in ultrasonic emission elicited by in utero exposure to this neuroleptic were markedly different from those produced by its administration during the early postnatal period. Moreover, adult male rats treated prenatally with haloperidol exhibited a significant increase in the intensity of ultrasonic 22 kHz post-ejaculatory calls emitted during sexual behaviour. The duration of the period of the 22 kHz calls emission was also significantly increased by haloperidol treatment. These results confirm that ultrasonic vocalization in rats is a sensitive indicator of subtle changes in adverse treatments administered during development.

Animals↗

Ultrasonic vocalization in response to unavoidable aversive stimuli in rats: effects of benzodiazepines.

The effects of two benzodiazepine derivatives (diazepam, 0.5-1 mg/kg; alprazolam, 1.25-2.5 mg/kg) on ultrasonic calling elicited in adult rats by unavoidable aversive stimuli (footshocks) were investigated. The results show that either diazepam or alprazolam affected the duration of ultrasonic calls. In particular, a significant decrease in the length of ultrasounds was found in the group of animals treated with these benzodiazepines. The effects of diazepam were counteracted by the benzodiazepine-antagonist Ro 15-1788. On the other hand, neither a neuroleptic agent, such as haloperidol (0.5-1 mg/kg), nor an antidepressant, such as desipramine (5-10 mg/kg) influenced the parameters of ultrasonic emission in this experimental situation. The present results suggest that ultrasonic vocalization in response to unavoidable aversive stimuli could be considered as a potential new tool for studying drugs with antianxiety properties.

Alprazolam↗

Mechanisms of neurotoxicity and their relationship to behavioral changes.

In this review some of the evidence relating behavioral alterations induced by 2 neurotoxic chemicals, lead acetate and methyl mercury is presented with an attempt to relate these changes to the underlying neurobiological mechanisms. In the case of neonatal lead poisoning, the results of the early behavioral studies were confounded by excessive lead concentrations resulting in undernutrition of the pups. Subsequent studies in both rodents and monkeys have shown that blood-lead concentrations comparable to those seen in children can induce behavioral alterations that may be related to hippocampal damage. In the case of methyl mercury which is a potent cytotoxic agent, prenatal exposure results in widespread cortical, and cerebellar alterations characterized by reduced myelination, delayed migration and loss of neurons. These morphological alterations are accompanied by permanent alterations in learning and memory as well as altered pharmacological sensitivity in catecholaminergic systems. Recommendations are made for better formulated behavioral and neurobiological assays in neurotoxicology in order to lead to a better understanding of the toxicity of chemicals.

Animals↗

Ontogenetic and pharmacological dissociation of various components of locomotor activity and habituation in the rat.

Sprague-Dawley-derived male rats were used to investigate locomotor activity and habituation in an open field as a joint function of developmental age (2-6 weeks), pattern of test exposure (single 30-min test vs three 5-min tests at 24-hr intervals), and treatment conditions (i.p. saline, d-amphetamine sulfate 1 mg/kg, or scopolamine hydrocloride 0.5 mg/kg). No-drug animals showed low activity levels in both tests at the end of the second week, intermediate response rates at the end of the third week, and a typical adult-like pattern at later ages (high initial activity followed by marked within-session or between-session habituation). Amphetamine effects varied considerably depending jointly on age and type of test. At the end of the second week, the drug hyperactivity was much more marked in successive brief tests than in the single extended test. One week later, the response increase was rather uniform in both tests. At the end of the fourth week, the sensitivity profile was reversed, consisting of a large drug effect in the extended test but not in successive brief tests. Scopolamine was still without effects at this age, while a typical hyperactivity was produced by the drug in 6-week-old animals. These data show that, at least in the rat strain used, the functional maturation of muscarinic regulatory systems is not a necessary condition either for the appearance of an adult-like response pattern, or for the occurrence of the age- and test-related changes of the amphetamine profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗