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S Chiavegatto

Publications and source records attributed to S Chiavegatto.

11 recordsLinked to original sources
PubMed2001

Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase.

Genetically engineered mice with targeted disruption of the neuronal nitric oxide synthase (nNOS) gene established the inhibitory role of nitric oxide (NO) in male impulsive aggressive behavior. This was later confirmed by using selective nNOS inhibitors in male wild-type mice. The molecular mechanisms accounting for the aggressive behavior caused by the lack of neuronally derived NO is not known. Recent studies suggest that central serotonergic neuronal circuits and particularly 5-HT(1A) and 5-HT(1B) receptors play a prominent role in the regulation of aggression. Accordingly, we investigated whether the aggressiveness caused by the lack of nNOS might be because of alterations in serotonergic function. We now demonstrate that the excessive aggressiveness and impulsiveness of nNOS knockout mice is caused by selective decrements in serotonin (5-HT) turnover and deficient 5-HT(1A) and 5-HT(1B) receptor function in brain regions regulating emotion. These results indicate an important role for NO in normal brain 5-HT function and may have significant implications for the treatment of psychiatric disorders characterized by aggressiveness and impulsivity.

5-Hydroxytryptophan↗
PubMed2001

Molecular basis of aggression.

Recent pharmacological and genetic studies have dramatically expanded the list of neurotransmitters, hormones, cytokines, enzymes, growth factors, and signaling molecules that influence aggression. In spite of this expansion, serotonin (5-HT) remains the primary molecular determinant of inter-male aggression, whereas other molecules appear to act indirectly through 5-HT signaling. We review evidence of interactions among these molecules and aggressive behavior. Slight modulations in 5-HT levels, turnover, and metabolism, or in receptor subtype activation, density, and binding affinity affect aggression. Activation of specific 5-HT receptors evokes distinct, but highly interacting, second messenger systems and multiple effectors. Understanding the interactions between 5-HT receptor subtypes should lead to novel insights into the molecular mechanisms of aggression.

Aggression↗
PubMed2000

A functional role for complex gangliosides: motor deficits in GM2/GD2 synthase knockout mice.

Although gangliosides are abundant molecular determinants on all vertebrate nerve cells (comprising approximately 1.5% of brain dry weight) their functions have remained obscure. We report that mice engineered to lack a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase), and which express only the simple ganglioside molecular species GM3 and GD3, develop significant and progressive behavioral neuropathies, including deficits in reflexes, strength, coordination, and balance. Quantitative indices of motor abilities, applied at 8 and 12 months of age, also revealed progressive gait disorders in complex ganglioside knockout mice compared to controls, including reduced stride length, stride width, and increased hindpaw print length as well as a marked reduction in rearing. Compared to controls, null mutant mice tended to walk in small labored movements. Twelve-month-old complex ganglioside knockout mice also displayed significant incidence of tremor and catalepsy. These comprehensive neurobehavioral studies establish an essential role for complex gangliosides in the maintenance of normal neural physiology in mice, consistent with a role in maintaining axons and myelin (Sheikh, K. A. , J. Sun, Y. Liu, H. Kawai, T. O. Crawford, R. L. Proia, J. W. Griffin, and R. L. Schnaar. 1999. Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proc. Natl. Acad. Sci. USA 96: 7532-7537), and may provide insights into the mechanisms underlying certain neural degenerative diseases.

Animals↗
PubMed1998

Nitric oxide synthase activity in the dorsal periaqueductal gray of rats expressing innate fear responses.

Immunohistochemical studies have shown nitric oxide synthase (NOS)-positive neurons in the dorsolateral sector of periaqueductal gray (PAG), a neural site known to be critical for the expression of defensive responses. In the present study, we first characterized the dorsal PAG (dPAG) NOS, and then examined NOS activity and cyclic GMP (cGMP) accumulation in the dPAG of rats exposed to a predator (cat) for 15 min. NOS activity evaluated by enzymatic conversion of [3H]arginine to [3H]citrulline in dPAG of exposed rats increased 14.6% and the cGMP radioimmunoassay showed an increase of 30.6% in relation to non-exposed rats. These results suggest an involvement of the NO/cGMP pathway in the dPAG during defensive responses.

Analysis of Variance↗
PubMed1998

Histamine and spontaneous motor activity: biphasic changes, receptors involved and participation of the striatal dopamine system.

The time- and dose-related effects of exogenous histamine on spontaneous motor activity and receptors involved were evaluated in male rats. Intracerebroventricular administration of histamine (5.4 and 54.3 nmol) produced a biphasic effect with initial transitory hypoactivity and later hyperactivity expressed by locomotion frequency in an open-field. The rearing frequencies were only reduced by all doses of histamine used. The histamine-induced hypoactivity was inhibited by the H3-antagonist thioperamide and was also induced by the H3-agonist N-alpha-methylhistamine. The histamine-induced hyperactivity phase was blocked by the H1-antagonist mepyramine. The H2-antagonist ranitidine increased locomotion and rearing frequencies. The participation of other neurotransmitters in the persistent hypokinetic effect induced by 135.8 nmol of histamine was determined by HPLC in the striatum and hypothalamus as counter-proof. A decreased DOPAC/DA ratio was observed only in the striatum. In the hypothalamus, low levels of 5HT were detected, probably not correlated with motor activity. In conclusion, the present results suggest that the exogenous histamine-induced hypoactivity response is probably due to activation of H3-receptors as heteroreceptors reducing the activity of the striatal dopaminergic system. This effect can partially overlap with the expression of the hyperactivity induced by H1-receptor activation. The participation of H2-receptors requires further investigation.

Animals↗
PubMed1997

Severe reduction of rat defensive behavior to a predator by discrete hypothalamic chemical lesions.

Nonspecific lesion and stimulation methods have suggested that the hypothalamus is critical for the expression of defensive behavior, although the organization of neural circuits mediating such behavior is unclear. In the rat hypothalamus, we found that increased Fos levels were restricted to specific cell groups following presentation of a stimulus (predator) known to elicit partly innate defensive responses. The dorsal premammillary nucleus showed the most striking increase in Fos levels, and cell body-specific chemical lesions therein virtually eliminated two major components of defensive behavior but increased exploratory behavior, suggesting that this caudal hypothalamic nucleus plays a critical role in the expression of behavioral responses sometimes critical for survival of the individual. We have previously shown that the Fos-responsive cell groups in the medial hypothalamus are interconnected in a neural system distinct from those mediating reproductive and ingestive behaviors.

Animals↗
PubMed1991

Effects of prenatal diphenhydramine exposure on dopaminergic function in adult rats.

Female pregnant rats were treated with 20.0 mg/kg diphenhydramine (DPH) or the same volume of saline solution (NaCl 0.9%), SC, daily during pregnancy. As adults, male pups were tested for stereotyped behavior in response to apomorphine (1 mg/kg, SC) administration. No differences between DPH-exposed and control rats were evident. In another group of rats, dopamine (DA) and homovanillic acid (HVA) levels were quantified in striatal samples. DA levels were equivalent, but increased levels of HVA were observed. Based upon these data we suggest that prenatal exposure to DPH, a histamine (H1) receptor antagonist, reduces presynaptic dopaminergic mechanisms without altering postsynaptic dopaminergic function in adulthood.

Animals↗
PubMed1991

Prenatal versus postnatal effects on offspring weight gain of rats exposed to diphenhydramine: a critical evaluation of fostering procedures in rats.

1. In order to evaluate the relative contribution of fostering procedures in the analysis of the development of rats prenatally exposed to diphenhydramine (20 mg/kg/day, sc) the weight gain of litters fostered or not by their biological mothers were examined from 2-21 days of age. 2. Maternal behavior and milk production were also assessed. 3. The results showed a decreased weight gain only in offspring fostered by mothers from different prenatal treatments and a lack of effects on maternal behavior and milk production. 4. It was concluded that the reduced weight of cross-fostered litters was mediated through an interference with postnatal mother-offspring interaction, which was not herein identified.

Animals↗
PubMed1989

Effects of prenatal diphenhydramine administration on sexual behavior in rats.

In order to study the involvement of the brain histamine system on the sexual behavior of rats prenatally exposed to the histamine H1 receptor blockader, diphenhydramine (DPD), the female lordotic response and male sexual behavior were analyzed. The results show that the lordotic response in the prenatal DPD-treated rats was increased in relation to control animals. Impairment of male sexual behavior was indicated by an increase in ejaculation latency, in the number of mounts and a decrease in the number of ejaculations up to 30 min after the first intromission. Prenatal exposure to DPD thus appears to alter female and male sexual behavior on reaching adulthood.

Animals↗
PubMedDate not supplied

Prenatal exposure of rats to diphenhydramine: effects on physical development, open field, and gonadal hormone levels in adults.

Diphenhydramine (DPH), a classical H1 receptor antagonist, has been used in pregnancy for the treatment of allergies, nausea, and vomiting. It has been reported that 10-20% of pregnant women take antihistamine-containing preparations at some point during pregnancy. The present study analyzed the influence of prenatal exposure to DPH of rats on: 1) maternal behavior and milk production of dams; 2) physical and reflexologic development of offspring; and 3) long-term effects on open field behaviors and gonadal hormone levels in offspring. Female pregnant rats were injected s.c., daily, with 20 mg/kg DPH or saline from embryonic day (E) 0 to 21. After delivery, maternal behavior was assessed and offspring physical and reflexologic development was examined. Open field activity of male and female rats was measured at 21 and 75 days of age and plasma hormone levels were evaluated in both sexes at 120 days of age. Neither maternal behavior nor milk production was affected by DPH treatment. Treated offspring showed an accelerated pinna unfolding, eye opening, and a delay of testes descent and vaginal opening. Both righting reflex and negative geotaxis development were accelerated, but prenatal exposure to DPH did not modify offspring locomotor activity. When tested as adults, a lack of sexual dimorphism in the open field activity of males and females was observed. No differences were observed between gonadal hormone levels of control and experimental groups of either sex. The findings suggest that prenatal DPH exposure influences physical and reflex development of rat pups.

Animals↗