Brain region-specific studies of the excitatory behavioral effects of morphine-3-glucuronide

This study was designed to determine in rats whether morphine-3-glucuronide (M3G) produces its neuro-excitatory effects most potently in the ventral hippocampus (as has been reported previously for subanalgesic doses of opioid peptides). Guide cannulae were implanted into one of seven regions of the rat brain: lateral ventricle; ventral, CA1 and CA2-CA3 regions of the hippocampus; amygdala; striatum or cortex. After a 7 day recovery period, rats received intracerebral injections of (i) M3G (1.1 or 11 nmol) (ii) DADLE ([D-Ala(2),D-Leu(5)]enkephalin), (45 nmol, positive controls) or (iii) vehicle (deionised water), and behavioral excitation was quantified over 80 min. High-dose M3G (11 nmol) evoked behavioral excitation in all brain regions but the onset, severity and duration of these effects varied considerably among brain regions. By contrast, low-dose M3G (1.1 nmol) evoked excitatory behaviors only when administered into the ventral hippocampus and the amygdala, with the most potent effects being observed in the ventral hippocampus. Prior administration of the nonselective opioid antagonists, naloxone and beta-funaltrexamine into the ventral hippocampus, markedly attenuated low-dose M3G's excitatory effects but did not significantly alter levels of excitation evoked by high-dose M3G. Naloxone given 10 min after M3G (1.1 or 11 nmol) did not significantly attenuate behavioral excitation. Thus, M3G's excitatory behavioral effects occur most potently in the ventral hippocampus as reported previously for subanalgesic doses of opioid peptides, and appear to be mediated through at least two mechanisms, one possibly involving excitatory opioid receptors and the other, non-opioid receptors.

Binding sites and actions of Tx1, a neurotoxin from the venom of the spider Phoneutria nigriventer, in guinea pig ileum

Tx1, a neurotoxin isolated from the venom of the South American spider Phoneutria nigriventer, produces tail elevation, behavioral excitation and spastic paralysis of the hind limbs after intracerebroventricular injection in mice. Since Tx1 contracts isolated guinea pig ileum, we have investigated the effect of this toxin on acetylcholine release, as well as its binding to myenteric plexus-longitudinal muscle membranes from the guinea pig ileum. [125I]-Tx1 binds specifically and with high affinity (Kd = 0.36 ± 0.02 nM) to a single, non-interacting (nH = 1.1), low capacity (Bmax 1.1 pmol/mg protein) binding site. In competition experiments using several compounds (including ion channel ligands), only PhTx2 and PhTx3 competed with [125I]-Tx1 for specific binding sites (K0.5 apparent = 7.50 x 10-4 g/l and 1.85 x 10-5 g/l, respectively). PhTx2 and PhTx3, fractions from P. nigriventer venom, contain toxins acting on sodium and calcium channels, respectively. However, the neurotoxin PhTx2-6, one of the isoforms found in the PhTx2 pool, did not affect [125I]-Tx1 binding. Tx1 reduced the [3H]-ACh release evoked by the PhTx2 pool by 33%, but did not affect basal or KCl-induced [3H]-ACh release. Based on these results, as well as on the homology of Tx1 with toxins acting on calcium channels (w-Aga IA and IB) and its competition with [125I]-w-Cono GVIA in the central nervous system, we suggest that the target site for Tx1 may be calcium channels.

Norepinephrine ignites local hot spots of neuronal excitation: how arousal amplifies selectivity in perception and memory

Arousal sometimes enhances and sometimes impairs perception and memory. In our Glutamate Amplifies Noradrenergic Effects (GANE) model, glutamate at active synapses interacts with norepinephrine released by the locus coeruleus to create local ‘hot spots’ of activity that enable the selective effects of arousal. This hot spot mechanism allows local cortical regions to self-regulate norepinephrine release based on current activation levels. In turn, hot spots bias global energetic delivery and functional network connectivity to enhance processing of high priority representations and impair processing of lower priority representations.

Behavioral and Antinociceptive Effects of Alfentanil, Butorphanol, and Flunixin in Horses

To determine the behavioral and antinociceptive effects of narcotic and non-narcotic analgesics administered by intravenous injection in horses, 10 thoroughbred mares weighing between 450 and 550 kg and ranging in age from 8 to 13 years old were analyzed. The effects of alfentanil, butorphanol, flunixin, and saline solution on the general activity of the horses were investigated by measuring spontaneous locomotor activity (SLA) and head height (HH) in two behavior stalls. The antinociceptive effects of alfentanil (0.02 mg kg-1), butorphanol (0.1 mg kg-1), flunixin meglumine (0.5 mg kg-1), and saline were determined by measuring skin twitch reflex latency (STRL) after thermal cutaneous nociceptive stimulation. A paired Student t-test was used to compare SLA and HH between the groups of horses receiving different doses of the same drug at various time points. The Tukey test was used to compare the antinociceptive effect of the treatments. Differences were considered significant when P value was <.05. Horses treated with opioid analgesics demonstrated excitation, as shown by a significant increase in SLA at all doses tested and by neighing and demonstrating attentive attitudes with movement of the ears, stereotypical walking, and ataxia in most of the animals. HH was elevated only in animals treated with alfentanil. Antinociception was observed at 5 and 30 minutes after administration of alfentanil and butorphanol, respectively. Increased SLA was observed at 30 and 90 minutes after administration of alfentanil and butorphanol, respectively. We observed no effect on antinociception in horses given flunixin. In conclusion, this study suggests that alfentanil has a faster onset and a shorter duration than butorphanol; however, both drugs are able to stimulate the central nervous system. © 2013 Elsevier Inc. All rights reserved.

Cognitive And Behavioral Heterogeneity In Genetic Syndromes.

this study aimed to investigate the cognitive and behavioral profiles, as well as the psychiatric symptoms and disorders in children with three different genetic syndromes with similar sociocultural and socioeconomic backgrounds. thirty-four children aged 6 to 16 years, with Williams-Beuren syndrome (n=10), Prader-Willi syndrome (n=11), and Fragile X syndrome (n=13) from the outpatient clinics of Child Psychiatry and Medical Genetics Department were cognitively assessed through the Wechsler Intelligence Scale for Children (WISC-III). Afterwards, a full-scale intelligence quotient (IQ), verbal IQ, performance IQ, standard subtest scores, as well as frequency of psychiatric symptoms and disorders were compared among the three syndromes. significant differences were found among the syndromes concerning verbal IQ and verbal and performance subtests. Post-hoc analysis demonstrated that vocabulary and comprehension subtest scores were significantly higher in Williams-Beuren syndrome in comparison with Prader-Willi and Fragile X syndromes, and block design and object assembly scores were significantly higher in Prader-Willi syndrome compared with Williams-Beuren and Fragile X syndromes. Additionally, there were significant differences between the syndromes concerning behavioral features and psychiatric symptoms. The Prader-Willi syndrome group presented a higher frequency of hyperphagia and self-injurious behaviors. The Fragile X syndrome group showed a higher frequency of social interaction deficits; such difference nearly reached statistical significance. the three genetic syndromes exhibited distinctive cognitive, behavioral, and psychiatric patterns.

Neurodevelopment Of Small-for-gestational Age Infants: Behavioral Aspects In First Year.

The purpose of this study was to compare the behavior of full-term small-for-gestational age (SGA) with full-term appropriate-for gestational age (AGA) infants in the first year of life. We prospectively evaluated 68 infants in the 2nd month, 67 in the 6th month and 69 in the 12th month. The Bayley Scales of Infant Development-II were used, with emphasis on the Behavior Rating Scale (BRS). The groups were similar concerning the item interest in test materials and stimuli; there was a trend toward differences in the items negative affect, hypersensitivity to test materials and adaptation to change in test materials. The mean of Raw Score was significantly lower for the SGA group in the items predominant state, liability of state of arousal, positive affect, soothability when upset, energy, exploration of objects and surroundings, orientation toward examiner. A lower BRS score was associated with the SGA group in the 2nd month.

Behavioral Changes Caused By Austrodiplostomum Spp. In Hoplias Malabaricus From The São Francisco River, Brazil.

Traira (Hoplias malabaricus) is a neotropical fish that is widely distributed in freshwater environments in South America. In the present study, we documented the occurrence of metacercariae of Austrodiplostomum spp. (Diplostomidae) in the eyes and cranial cavity of H. malabaricus and described parasite-induced behavioral changes in the host. The fish were collected from the upper São Francisco River, in the Serra da Canastra mountain range, Minas Gerais, transported alive to the laboratory, observed for 2 weeks, and subsequently examined for parasites. Of the 35 fish examined, 28 (80 %) had free metacercariae in the vitreous humor (mean intensity=95.4; mean abundance=76.3), and 24 (68.57 %) had free metacercariae in the cranial cavity, mainly concentrated below the floor of the brain, at the height of the ophthalmic lobe (mean intensity=12.91; mean abundance=8.85). Specimens of H. malabaricus with a high intensity of infection in the brain displayed changes in swimming behavior.

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD), increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL) from postnatal day (PND) 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39), the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg) or MPD (10 mg/kg); MPD pretreated rats received MPD (10 mg/kg). Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood). To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg) or nicotine (0.4 mg/kg). All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

Behavioral alarm treatment for nocturnal enuresis

PURPOSES: To investigate the efficacy of alarm treatment in a sample of Brazilian children and adolescents with nocturnal enuresis and relate treatment success to age and type of clinical support. MATERIALS AND METHODS: During 32 weeks, 84 children and adolescents received alarm treatment together with weekly psychological support sessions for individual families or groups of 5 to 10 families. RESULTS: 71% of the participants achieved success, defined as 14 consecutive dry nights. The result was similar for children and adolescents and for individual or group support. The time until success was shorter for participants missing fewer support sessions. CONCLUSIONS: Alarm treatment was effective for the present sample, regardless of age or type of support. Missing a higher number of support sessions, which may reflect low motivation for treatment, increased the risk of failure.

Changes in parents' and self-reports of behavioral problems in Brazilian adolescents after behavioral treatment with urine alarm for nocturnal enuresis

PURPOSE: Compare parents' reports of youth problems (PRYP) with adolescent problems self-reports (APSR) pre/post behavioral treatment of nocturnal enuresis (NE) based on the use of a urine alarm. MATERIALS AND METHODS: Adolescents (N = 19) with mono-symptomatic (primary or secondary) nocturnal enuresis group treatment for 40 weeks. Discharge criterion was established as 8 weeks with consecutive dry nights. PRYP and APSR were scored by the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR). RESULTS: Pre-treatment data: 1) Higher number of clinical cases based on parent report than on self-report for Internalizing Problems (IP) (13/19 vs. 4/19), Externalizing Problems (EP) (7/19 vs. 5/19) and Total Problem (TP) (11/19 vs. 5/19); 2) Mean PRYP scores for IP (60.8) and TP (61) were within the deviant range (T score ≥ 60); while mean PRYP scores for EP (57.4) and mean APSR scores (IP = 52.4, EP = 49.5, TP = 52.4) were within the normal range. Difference between PRYP' and APSR' scores was significant. Post treatment data: 1) Discharge for majority of the participants (16/19); 2) Reduction in the number of clinical cases on parental evaluation: 9/19 adolescents remained within clinical range for IP, 2/19 for EP, and 7/19 for TP. 3) All post-treatment mean scores were within the normal range; the difference between pre and post evaluation scores was significant for PRYP. CONCLUSIONS: The behavioral treatment based on the use of urine alarm is effective for adolescents with mono-symptomatic (primary and secondary) nocturnal enuresis. The study favors the hypothesis that enuresis is a cause, not a consequence, of other behavioral problems.

Behavioral and Autonomic Responses to Acute Restraint Stress Are Segregated within the Lateral Septal Area of Rats

Background: The Lateral Septal Area (LSA) is involved with autonomic and behavior responses associated to stress. In rats, acute restraint (RS) is an unavoidable stress situation that causes autonomic (body temperature, mean arterial pressure (MAP) and heart rate (HR) increases) and behavioral (increased anxiety-like behavior) changes in rats. The LSA is one of several brain regions that have been involved in stress responses. The aim of the present study was to investigate if the neurotransmission blockade in the LSA would interfere in the autonomic and behavioral changes induced by RS. Methodology/Principal Findings: Male Wistar rats with bilateral cannulae aimed at the LSA, an intra-abdominal datalogger (for recording internal body temperature), and an implanted catheter into the femoral artery (for recording and cardiovascular parameters) were used. They received bilateral microinjections of the non-selective synapse blocker cobalt chloride (CoCl(2), 1 mM/ 100 nL) or vehicle 10 min before RS session. The tail temperature was measured by an infrared thermal imager during the session. Twenty-four h after the RS session the rats were tested in the elevated plus maze (EPM). Conclusions/Significance: Inhibition of LSA neurotransmission reduced the MAP and HR increases observed during RS. However, no changes were observed in the decrease in skin temperature and increase in internal body temperature observed during this period. Also, LSA inhibition did not change the anxiogenic effect induced by RS observed 24 h later in the EPM. The present results suggest that LSA neurotransmission is involved in the cardiovascular but not the temperature and behavioral changes induced by restraint stress.

Predictive factors of non-deterioration of glucose tolerance following a 2-year behavioral intervention

Aim: To identify predictive factors associated with non-deterioration of glucose metabolism following a 2-year behavioral intervention in Japanese-Brazilians. Methods: 295 adults (59.7% women) without diabetes completed 2-year intervention program. Characteristics of those who maintained/improved glucose tolerance status (non-progressors) were compared with those who worsened (progressors) after the intervention. In logistic regression analysis, the condition of non-progressor was used as dependent variable. Results: Baseline characteristics of non-progressors (71.7%) and progressors were similar, except for the former being younger and having higher frequency of disturbed glucose tolerance and lower C-reactive protein (CRP). In logistic regression, non-deterioration of glucose metabolism was associated with disturbed glucose tolerance impaired fasting glucose or impaired glucose tolerance - (p < 0.001) and CRP levels <= 0.04 mg/dL (p = 0.01), adjusted for age and anthropometric variables. Changes in anthropometry and physical activity and achievement of weight and dietary goals after intervention were similar in subsets that worsened or not the glucose tolerance status. Conclusion: The whole sample presented a homogeneous behavior during the intervention. Lower CRP levels and diagnosis of glucose intolerance at baseline were predictors of non-deterioration of the glucose metabolism after a relatively simple intervention, independent of body adiposity.

Structure of (46)Ti at low excitation energy

The nucleus (46)Ti has been studied with the reaction (42)Ca((7)Li,p2n)(46)Ti at a bombarding energy of 31 MeV. Thin target foils backed with a thick Au layer were used. Five new levels of negative parity were observed. Several lifetimes have been determined with the Doppler shift attenuation method. Low-lying experimental negative-parity levels are assigned to three bands with K(pi) = 3, 0, and 4, which are interpreted in terms of the large-scale shell model, considering particle-hole excitations from d(3/2) and s(1/2) orbitals. Shell model calculations were performed using a few effective interactions. However, good agreement was not achieved in the description of either negative- or positive-parity low-lying levels.

Electric Field Effects in the Excitation of Cold Rydberg-Atom Pairs

In this work, we study the role of the ac Stark effects on the excitation of nS(1/2) cold Rydberg atoms produced in a rubidium magneto-optical trap. We have observed an atomic population in the nP(3/2) state after excitation of nS(1/2) for 29 <= n <= 37. Such an observation is normally attributed to binary collisions; however, the interaction between Rb nS(1/2) atoms is repulsive. To explain our results, the dipole-dipole interaction and ac Stark shifts from the excitation laser must be considered. We find that the Rydberg-atom-pair state asymptotically correlating to nP(3/2)+(n-1)P(3/2) is excited directly.

Quantum yield excitation spectrum (UV-visible) of CdSe/ZnS core-shell quantum dots by thermal lens spectrometry

A recently developed thermal lens spectrometry configuration has been used to study CdSe/ZnS core-shell quantum dots (QDs) suspended in toluene and tetrahydrofuran (THF) solvents. The special features of this configuration make it very attractive to measure fluorescence quantum yield (eta) excitation spectrum since it simplifies the measurement procedure and consequently improve the accuracy. Furthermore, the precision reached is much higher than in conventional photoluminescence (PL) technique. Two methods, called reference sample and multiwavelength have been applied to determine eta, varying excitation wavelength in the UV-visible region (between 335-543 nm). The eta and PL spectra are practically independent of the excitation wavelength. For CdSe/ZnS QDs suspended in toluene we have obtained eta=76 +/- 2%. In addition, the aging effect on eta and PL has been studied over a 200 h period for QDs suspended in THF. (C) 2010 American Institute of Physics. [doi:10.1063/1.3343517]