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Biomedical subjects

Richard H Melloni

Publications and source records attributed to Richard H Melloni.

12 recordsLinked to original sources

Serotonin type 3 receptors stimulate offensive aggression in Syrian hamsters.

Hamsters repeatedly exposed to cocaine during adolescence display high levels of offensive aggression compared to saline-treated littermates. The escalated offensive phenotype observed in adolescent cocaine-treated animals is modulated by serotonin (5-HT) signaling and can be suppressed by inhibiting 5-HT type 3 receptors, suggesting that these receptors might play an important role in the aggression-stimulating effects of adolescent cocaine exposure. The current study examined this hypothesis and extended earlier studies investigating the relationship between 5HT(3) receptor neural signaling and the offensive response patterns of aggressive, adolescent cocaine-treated animals compared to non-aggressive, saline-treated littermates. Adolescent cocaine-treated hamsters and saline-treated littermates were tested for offensive aggression after the administration of either the 5-HT(3) antagonist 3-tropanylindole-3-carboxylate methiodide (tropisetron) or the 5-HT(3) agonist 1-(m-chlorophenyl)-biguanide hydrochloride (mCPBG). Tropisetron significantly reduced the high levels of offensive responding observed in adolescent cocaine-treated animals, whereas treatment with the 5-HT(3) receptor agonist mCPBG failed to affect the escalated offensive response. Conversely, tropisetron failed to affect very low, baseline levels of aggressive responding seen in adolescent saline-treated animals, while 5-HT(3) receptor activation via mCPBG triggered highly escalated levels of offensive aggression in these animals. Together, these data support a stimulatory role for 5-HT(3) neural signaling in offensive aggression.

Age Factors↗

Proactive and reactive aggression in referred children and adolescents.

Investigating different types of aggression is important to facilitate a better understanding of excessive maladaptive aggression in referred youth. Using regression analysis, the authors investigated demographic, historical, diagnostic, and treatment correlates of proactive aggression and reactive aggression in a heterogeneous population (N = 323) of psychiatrically referred youths. Ratings of proactive and reactive aggression significantly correlated with more established measures of aggression. Results suggest the importance of hyperactive/impulsive behavior, disruptive behavior disorders, and self-reported hostility in youths with both reactive and proactive aggression. Substance use disorders, a family history of substance abuse, and family violence were specifically associated with proactive aggression. Younger age and a history of abuse were correlated with reactive aggression. Implications for clinical interventions and future research are discussed.

Adolescent↗

Serotonin type 3 receptors modulate the aggression-stimulating effects of adolescent cocaine exposure in Syrian hamsters (Mesocricetus auratus).

Repeated cocaine (0.5 mg/kg) exposure throughout adolescence stimulates offensive aggression in hamsters. These studies examined whether the cocaine-induced aggressive response was regulated by serotonin Type 3 (5-HT(3)) receptor activity and correlated with altered 5-HT(3) receptor expression. Cocaine-treated Syrian hamsters (Mesocricetus auratus) were tested for aggression after the administration of either the 5-HT(3) antagonist 3-tropanylindole-3-carboxylate methiodide (tropisetron; 0.01-1.20 mg/kg) or the 5-HT(3) agonist l-(m-chlorophenyl)-biguanide hydrochloride (mCPBG; 5.0-15.0 mg/kg), alone or in combination. Tropisetron alone dose dependently reduced cocaine-induced aggression, with a significant reduction at 0.3 mg/kg, whereas mCPBG was ineffective. mCPBG administered prior to tropisetron required a higher dose (1.2 mg/kg) of antagonist to block aggression, indicating a selective 5-HT(3) effect. Cocaine-treated hamsters showed altered 5-HT-sub-3 immunoreactivity in several brain areas implicated in aggression control. These data support a role for 5-HT(3) receptors in adolescent cocaine-induced aggression.

Age Factors↗

Glutamic acid decarboxylase (GAD65) immunoreactivity in brains of aggressive, adolescent anabolic steroid-treated hamsters.

Chronic anabolic-androgenic steroid (AAS) treatment during adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study assessed whether adolescent AAS exposure influenced the immunohistochemical localization of glutamic acid decarboxylase (GAD65), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), in areas of hamster brain implicated in aggressive behavior. Hamsters were administered high dose AAS throughout adolescence, scored for offensive aggression, and then examined for differences in GAD65 puncta to regions of the hamster brain important for aggression. When compared with control animals, aggressive AAS-treated hamsters showed significant increases in the area covered by GAD65 immunoreactive puncta in several of these aggression regions, including the anterior hypothalamus, ventrolateral hypothalamus, and medial amygdala. Conversely, aggressive AAS-treated hamsters showed a significant decrease in GAD65-ir puncta in the lateral septum when compared with oil-treated controls. However, no differences in GAD65 puncta were found in other aggression areas, such as the bed nucleus of the stria terminalis and central amygdala. Together, these results support a role for altered GAD65 synthesis and function in adolescent AAS-facilitated offensive aggression.

Aggression↗

Gender differences in reactive and proactive aggression.

The purpose of our investigation was to study gender differences in proactive and reactive aggression in a sample of 323 clinically referred children and adolescents (68 females and 255 males). Proactive aggression and reactive aggression were assessed using the Proactive/Reactive Aggression Scale. Demographic, historical, family, diagnostic, and treatment variables were entered into stepwise regression analyses to determine correlates of proactive and reactive aggression in males and females. Results reveal high rates of aggression in both males and females in the sample. Self reported drug use, expressed hostility, and experiences of maladaptive parenting were correlated with proactive aggression for both genders. Hyperactive/impulsive behaviors were correlated with male reactive aggression. An early age of traumatic stress and a low verbal IQ were correlated with female proactive aggression. Gender differences in correlates of proactive and reactive aggression may provide possible targets for research, prevention, and treatment efforts focused on reducing maladaptive aggression in clinically referred youth.

Adolescent↗

Aggressive behavior in abused children.

Our objective was to investigate the relationship between a lifetime history of traumatic stress, defined as physical and/or sexual abuse and aggression and psychosocial functioning in a sample of clinically referred and nonclinically referred children and adolescents. This is a retrospective case comparison study. Three groups of children were identified, assessed, matched for age, and partially matched for gender. Children clinically referred to residential treatment with a history of abuse (N = 29) were compared with children clinically referred to residential treatment without a history of abuse (N = 29), and a nonclinical group of children residing in the community (N = 29). Variables investigating specific types of aggression, IQ, and psychopathology were assessed across the three groups. Clinically referred children scored worse on all measures compared with nonclinical community children. Clinically referred abused children scored higher on measures of aggression and significantly higher on measures of reactive aggression and verbal aggression than clinically referred nonabused children. Clinically referred abused children had significantly lower verbal IQ scores than clinically referred nonabused children, but no difference in psychopathology. Results support the importance of assessing specific types of aggression in samples of traumatized youths. Verbal information processing may be especially vulnerable in abused children and adolescents and enhance vulnerability to aggressive responding.

Adolescent↗

Adolescent cocaine exposure and offensive aggression: involvement of serotonin neural signaling and innervation in male Syrian hamsters.

Repeated low-dose cocaine treatment (0.5 mg/kg/day) during adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study assessed whether adolescent cocaine-facilitated offensive aggression was inhibited by increased serotonin activity and if cocaine exposure during this developmental period influenced serotonin development in the primary aggression areas of hamster brain. In a first experiment, hamsters were treated with low doses of cocaine throughout adolescence and then scored for offensive aggression following the systemic administration of vehicle or fluoxetine, a selective serotonin reuptake inhibitor. Vehicle-treated hamsters showed high levels of offensive aggression, while treatment with fluoxetine inhibited the cocaine-facilitated aggressive response. Only one out of ten fluoxetine-treated animals both attacked and bit intruders, compared to nine out of ten saline-treated animals. In a second experiment, hamsters were administered low doses of cocaine or saline throughout adolescence, tested for offensive aggression, and then examined for differences in serotonin afferent innervation to regions of the hamster brain implicated in aggressive responding. Aggressive cocaine-treated hamsters showed significant reductions (35-50%) in the number of serotonin immunoreactive varicosities and fibers in several aggression areas, including the anterior hypothalamus, lateral septum, medial amygdala, and bed nucleus of the stria terminalis. Together, these results support a role for serotonin innervation and function in adolescent cocaine-facilitated offensive aggression.

Aggression↗

Repeated anabolic-androgenic steroid treatment during adolescence increases vasopressin V(1A) receptor binding in Syrian hamsters: correlation with offensive aggression.

Repeated anabolic-androgenic steroid treatment during adolescence increases hypothalamic vasopressin and facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study investigated whether anabolic-androgenic steroid exposure during this developmental period influenced vasopressin V(1A) receptor binding activity in the hypothalamus and several other brain areas implicated in aggressive behavior in hamsters. To test this, adolescent male hamsters were administered anabolic steroids or sesame oil throughout adolescence, tested for offensive aggression, and examined for differences in vasopressin V(1A) receptor binding using in situ autoradiography. When compared with control animals, aggressive, adolescent anabolic steroid-treated hamsters showed significant increases (20-200%) in the intensity of vasopressin V(1A) receptor labeling in several aggression areas, including the ventrolateral hypothalamus, bed nucleus of the stria terminalis, and lateral septum. However, no significant differences in vasopressin V(1A) receptor labeling were found in other brain regions implicated in aggressive responding, most notably the lateral zone from the medial preoptic area to anterior hypothalamus and the corticomedial amygdala. These data suggest that adolescent anabolic steroid exposure may facilitate offensive aggression by increasing vasopressin V(1A) receptor binding in several key areas of the hamster brain.

Aggression↗

Social stress does not alter the expression of sensitization to cocaine.

The effects of chronic social stress on behavioral sensitization to cocaine were investigated in the Syrian hamster. Adolescent animals received either 15 mg/kg i.p. of cocaine or saline twice per day for 7 consecutive days. Two weeks following the last injection (young adulthood), they were given a challenge dose of 5 mg/kg i.p. of cocaine and scored for locomotion. Motor activity was significantly greater in cocaine-treated animals, demonstrating sensitization to this psychostimulant. Following the results of the first study, another group of adolescent animals was exposed to either a novel clean cage (control) or an aggressive resident male hamster (social stress) for 15 min following an injection of cocaine (20 mg/kg i.p. once daily) or saline for 7 consecutive days. The groups were as follows: Social Stress/Cocaine (SSC), No Social Stress/Cocaine (NSSC), Social Stress/Saline (SSS) and No Social Stress/Saline (NSSS). Two weeks following the last injection (Day 21), all animals were given a challenge dose of cocaine (5 mg/kg i.p.) and were rescored for locomotion. At that time, the suppressive effect of stress on locomotion was no longer detectable, as the expression of sensitization was observed in the NSSC but not in the SSC group. These results suggest that chronic social stress administered during adolescence does not cross-sensitize with cocaine in young adult hamsters.

Animals↗

Serotonin modulates offensive attack in adolescent anabolic steroid-treated hamsters.

Chronic anabolic-androgenic steroid (AAS) treatment during adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study assessed whether adolescent AAS-facilitated offensive attack was modulated by serotonin (5-HT) and if AAS exposure during this developmental period influenced 5-HT innervation to areas of hamster brain implicated in aggressive behavior. In a first experiment, hamsters were administered high-dose AAS throughout adolescence, and then scored for offensive attack following the systemic administration of saline or fluoxetine, a selective 5-HT reuptake inhibitor. Saline-treated hamsters showed high levels of offensive attack, while treatment with fluoxetine attenuated the AAS-facilitated aggressive response. In a second experiment,were administered high-dose AAS or sesame oil throughout adolescence, tested for offensive attack and then examined for differences in 5-HT innervation to areas of the hamster brain important for aggression. Aggressive AAS-treated hamsters showed significant reductions in the number of 5-HT immunoreactive (5-HT-ir) varicosities and fibers in several of these areas, most notably the anterior hypothalamus (AH), ventrolateral hypothalamus (VLH) and medial amygdala (MeA). However, no differences in 5-HT afferent innervation were found in other aggression areas, such as the bed nucleus of the stria terminalis (BNST) and lateral septum (LS). Together, these results support a role for altered 5-HT innervation and function in adolescent AAS-facilitated offensive aggression.

Aggression↗

Psychopharmacology and aggression. I: A meta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD.

OBJECTIVE: To determine by meta-analysis the effect size for stimulants on overt and covert aggression-related behaviors in children with attention-deficit/hyperactivity disorder (ADHD), separately from stimulant effects on the core symptoms of ADHD. METHOD: A review of the literature from 1970 to 2001 revealed 28 studies meeting inclusion/exclusion criteria for meta-analysis. These studies yielded 28 independent effects of overt aggression and 7 independent effects of covert aggression. RESULTS: The overall weighted mean effect size was 0.84 for overt and 0.69 for covert aggression related behaviors in ADHD. Comorbid conduct disorder is associated with diminishing stimulant effect size for overt aggression. CONCLUSION: Stimulant effects for aggression-related behaviors in ADHD have effect sizes similar to those for the core symptoms of ADHD.

Adolescent↗

What does getting better mean? Child improvement and measure of outcome in residential treatment.

A single-sample, within-subject descriptive study was completed to ascertain individual subject characteristics associated with outcome for 87 youths discharged from a residential treatment facility. Two different methods of assessing outcome were also compared. Variables assessing a history of abuse and internalizing psychopathology at admission to residential care were associated with outcome. Low levels of staff agreement were found on the 2 outcome measures. Implications for acute residential care are discussed.

Adaptation, Psychological↗