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Nucleus accumbens muscarinic receptors in the control of behavioral depression: antidepressant-like effects of local M1 antagonist in the Porsolt swim test.

Systemically administered cholinomimetics or cholinesterase inhibitors can depress behavior in humans and animals, whereas antimuscarinic agents reverse this effect or even produce euphoria. Although these effects have been well documented, the specific brain regions that mediate them remain largely unknown. In the present experiments, muscarinic agonists and antagonists were locally injected into the nucleus accumbens of female Sprague-Dawley rats to test for their effects on behavioral depression in the Porsolt swim test and locomotor activity. Local, microinjections of the drugs in the accumbens elicited behaviors that were similar to the systemic effects reported in other studies. Injection of the non-specific agonist arecoline (40 and 80 microg) dose-dependently inhibited swimming and escape behavior. This may be mediated in part by accumbens M1 receptors because blocking these receptors with the specific antagonist pirenzepine (17.5 and 35.0 microg) did the opposite by increasing swimming. Gallamine (0.13, 0.44, and 0.88 microg), an antagonist at M2 receptors, dose-dependently decreased swimming. Two-way microdialysis suggested that this was in part due to the release of ACh by blocking M2 autoreceptors. Scopolamine, a mixed M1/M2 receptor antagonist, also released ACh but did not decrease swimming, probably because the M1 receptors were blocked; the drug (1.0 microg) increased swimming time, much like pirenzepine. With the exception of arecoline, none of the drugs significantly affected locomotor activity in a photocell cage. Arecoline (40 microg), which had decreased swimming, reduced activity. The present study suggests that muscarinic receptors in the nucleus accumbens can control immobility in the Porsolt swim test. The onset of immobility may depend on the activation of post-synaptic M1 receptors.

Acetylcholine↗

Effects of drugs on stimulus control of behavior. III. Analysis of effects of pentobarbital and d-amphetamine.

Key-peck responses of pigeons on one of two keys were reinforced intermittently under a multiple fixed-interval schedule. In one component of the schedule, a houselight provided general illumination of the experimental chamber, and responses on a red key produced food according to a 5-min fixed-interval schedule. In the alternate component, the houselight was off and responses on an amber key produced food according to the 5-min fixed-interval schedule. Each response randomly (P = .5) alternated the positions of the key colors (right or left) and the two components (houselight on or off) alternated in a mixed sequence. Thus, there were two sources of discriminative control over responding: 1) the presence or absence of the houselight and 2) the key colors. Stimulus control was assessed by comparing the relative frequencies of red-key responses in the presence and absence of the houselight. Pentobarbital decreased stimulus control of responding at intermediate (3.0-10.0 mg/kg) doses that did not appreciably alter average rates of responding. Whereas d-amphetamine decreased stimulus control only at high doses (3.0-5.6 mg/kg) that also substantially decreased response rates. The results of subsequent studies suggested that the two drugs primarily affected stimulus control exerted by the colors of the response keys. Furthermore, the effects on stimulus control produced by the two drugs were modified by a number of environmental conditions, in particular those that alter the degree of stimulus control existing before drug administration.

Animals↗

Adenosine and behavioral state control: adenosine increases c-Fos protein and AP1 binding in basal forebrain of rats.

In several brain areas, extracellular adenosine (AD) levels are higher during waking than sleep and during prolonged wakefulness AD levels in the basal forebrain increase progressively. Similarly, c-Fos levels in several brain areas are higher during waking than sleep and remain elevated during prolonged wakefulness. In the present study, we investigated the effect of extracellular AD levels on c-Fos protein and activator protein-1 (AP1) binding in the basal forebrain of rats. Increased levels of extracellular AD were induced either by keeping the animals awake, or by local perfusion of AD into the basal forebrain. During prolonged wakefulness extracellular AD concentration was monitored using in vivo microdialysis. The effect of AD perfusion on the behavioral states was recorded using polysomnography. At the end of the perfusion period the basal forebrain tissue was analyzed for the levels of c-Fos protein and AP1 binding. In vivo microdialysis measurements showed an increase in AD levels with prolonged wakefulness. Unilateral perfusion of AD (300 microM) increased non-REM sleep and delta power (0.5 to 4 Hz) when compared to rats perfused with artificial CSF. The levels of c-Fos protein and the AP1 DNA binding were high in the basal forebrain of both sleep-deprived animals and in animals perfused with AD. The results suggest that AD might mediate, at least in part, the long term effects of sleep deprivation by inducing c-Fos protein and subsequent AP1 binding.

Adenosine↗

Factorial validity and invariance of questionnaires measuring social-cognitive determinants of physical activity among adolescent girls.

BACKGROUND: There are few theoretically derived questionnaires of physical activity determinants among youth, and the existing questionnaires have not been subjected to tests of factorial validity and invariance. The present study employed confirmatory factor analysis (CFA) to test the factorial validity and invariance of questionnaires designed to be unidimensional measures of attitudes, subjective norms, perceived behavioral control, and self-efficacy about physical activity. METHODS: Adolescent girls in eighth grade from two cohorts (N = 955 and 1,797) completed the questionnaires at baseline; participants from cohort 1 (N = 845) also completed the questionnaires in ninth grade (i.e., 1-year follow-up). Factorial validity and invariance were tested using CFA with full-information maximum likelihood estimation in AMOS 4.0. Initially, baseline data from cohort 1 were employed to test the fit and, when necessary, to modify the unidimensional models. The models were cross-validated using a multigroup analysis of factorial invariance on baseline data from cohorts 1 and 2. The models then were subjected to a longitudinal analysis of factorial invariance using baseline and follow-up data from cohort 1. RESULTS: The CFAs supported the fit of unidimensional models to the four questionnaires, and the models were cross-validated, as indicated by evidence of multigroup factorial invariance. The models also possessed evidence of longitudinal factorial invariance. CONCLUSIONS: Evidence was provided for the factorial validity and the invariance of the questionnaires designed to be unidimensional measures of attitudes, subjective norms, perceived behavioral control, and self-efficacy about physical activity among adolescent girls.

Adolescent↗

Understanding the intention of gay and bisexual men to take the HIV antibody test.

This study offers an explanation for the intention of 1,512 gay and bisexual men to be tested for the HIV antibody. Participants were recruited through 125 gay-identified venues (bars, bathhouses, community dances) across Canada. Self-administered questionnaires assessed respondents' intention to take the test in the next year, predictor variables (e.g., attitudes, the perceived social norm of the gay community, perceived behavioral control, and other constructs such as reasons for not being tested and importance of aspects of the test such as confidentiality), and sociodemographic variables. For this analysis, two groups were formed: men who had taken the HIV test in the past with negative or unknown results (Group A) and men who had not taken the test (Group B). The proportions of men who intended to take the test in the next year were 84.8% and 53.3% for groups A and B, respectively. For both groups, logistic regression indicated that the most important factors explaining intention were attitudes toward taking the test and perceived behavioral control. Additional variables specific to each group also contributed to explain intention. Thus, to enhance test-seeking among this population requires a consistent program of health education and facilitative policies.

AIDS Serodiagnosis↗

Perception of spectrally and temporally complex sounds by the goldfish (Carassius auratus).

Behavioral studies on complex sound perception in goldfish were carried out in order to help determine what, if any, differences exist between the sense of hearing of fishes and other vertebrates. A stimulus generalization paradigm was used with classical conditioning in three experiments to determine: (1) the perceptual relations between a pure tone and harmonic complexes having a fundamental frequency equal to that of the tone; (2) the combined effects on perception of pulse repetition rate and spectral envelope; and (3) whether goldfish can be shown to identify a complex source when presented simultaneously with another complex source. Experiment 1 showed that the perceptions of tones and harmonic complexes differ profoundly even for the cases in which they have common periodicities and frequency components. Experiment 2 demonstrated that pulse repetition rate and spectral location simultaneously control behavior, and that repetition rate exerts behavioral control independent of spectral location. Experiment 3 indicates that goldfish did not 'hear out' or analyze a complex target source within a mixture of complex sources. In general, goldfish appear to be aware of multiple acoustic dimensions of complex sounds, suggesting both pitch-like and timbre-like perceptual dimensions. These results do not permit a qualitative distinction between the sense of hearing of goldfish and that of other vertebrates.

Acoustic Stimulation↗

In vitro degradation and controlled release behavior of D,L-PLGA50 and PCL-b-D,L-PLGA50 copolymer microspheres.

Blank and bovine serum albumin (BSA)-loaded microspheres based on poly(lactic-acid-alt-glycolic acid) (D,L-PLGA50) and poly(epsilon-caprolactone)-b-poly(lactic-acid-alt-glycolic acid) (PCL-b-D,L-PLGA50) were successfully fabricated using water-in-oil-in-water (w/o/w) double-emulsion extraction/evaporation technique. In vitro degradation of the blank microspheres was characterized by techniques including nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The PCL-b-D,L-PLGA50 copolymer (Mn: number-average molecular weight, Mw: weight-average molecular weight, Mn=44800, Mw/Mn=MWD=1.24, epsilon-caprolactone (CL) %=20.4% in molar ratio) had similar rate of molecular weight reduction compared with the D,L-PLGA50 copolymer before 5 weeks of in vitro degradation. The BSA % loading efficiency of microspheres was mainly controlled by both block copolymer composition and macromolecular architecture, while the sequence structure and the molecular weight of copolymer had no apparent effect on it. Significantly, The PCL-b-D,L-PLGA50 copolymer microspheres showed good release profiles with a nearly constant release during 20-110 days.

Animals↗

[The neurotransmitter basis of mollusk behavior: the control of the choice between exploratory and defensive responses to the presentation of an unknown object].

The role of serotonin and opioid peptides in decision making was studied in the pond snail Lymnaea stagnalis. It was shown that 5-HTP increased the number of searching responses to a sudden presentation of a novel object. Opiate antagonist naloxone decreased the number of searching responses and increased the number of defensive and escape reactions. The effect of 5-HTP and naloxone on decision making appear to be coordinated with their effects on their behavioural state.

5-Hydroxytryptophan↗

d-Amphetamine differentially affects low, but not high response rates of male and female Wistar rats.

The present experiments investigated sex differences in the effects of d-amphetamine on schedule-controlled behavior. Male and female Wistar rats were exposed to either a differential reinforcement of low rate 15 s schedule, or a differential reinforcement of high rate 0.75 s schedule and challenged with different doses of d-amphetamine (0.2, 0.4, 0.8, 1.6 and 3.2 mg/kg). d-Amphetamine in low to moderate doses increased low response rates. High doses of d-amphetamine decreased low and high response rates in both males and females. The response rate increasing effects of d-amphetamine on low baseline rates were significantly higher for females than for males. Sex differences for high baseline rates were not observed. The results of these experiments show not only that hormonal and neurochemical variables influence the effects of d-amphetamine administration on schedule-controlled behavior, but also that environmental contingencies maintaining the behavior can modify these effects.

Animals↗

Dissection of the sets of genes that control the behavior of biglycan-deficient pre-osteoblasts using oligonucleotide microarrays.

Biglycan (bgn) is a small leucine-rich proteoglycan (SLPR) that is enriched in the extracellular matrix of skeletal tissues. Bgn-deficient mice develop age-related osteopenia with a phenotype that resembles osteoporosis. In order to identify sets of genes that play a key role in the skeletal abnormality, we determined the global gene expression patterns in bgn-deficient (bgn-KO) pre-osteoblasts using oligonucleotide microarray technology. Calvarial cells were harvested from newborn mice and cultured in the presence or absence of BMP-4 for 7 days. The total RNA was purified, labeled and hybridized to Affymetrix chips (U74A), and analyzed with a software program called GeneSpring. Our data suggested that biglycan regulates the activity of osteoblastic progenitors through sets of genes associated with cell cycle, cell growth, and differentiation. The biological outcome from the altered expression of these genes could cause a defect in the quantity and quality of osteoblastic progenitors, which could contribute to the development of age-related osteopenia in bgn-KO mice. Moreover, the data from this approach also revealed that biglycan deficiency affected the genes that control inflammation, immune response, and growth of tumor cells. These are new and unexpected findings that lead to the formation of new paradigms for biglycan function. Based on these findings, we propose that the reduction of this small proteoglycan with aging may increase the risk of infection and autoimmune diseases, impair wound healing, and cause higher incidences of malignancy. This study provides a broad and deep foundation for understanding SLRP function at a more complex level.

Animals↗

Schedule-controlled operant behavior of rats during 1,1,1-trichloroethane inhalation: relationship to blood and brain solvent concentrations.

The central nervous system is the principal target of 1,1,1-trichloroethane (TRI), and several studies of this volatile solvent have demonstrated effects on learned animal behaviors. There have been few attempts, however, to quantitatively relate such effects to blood or target organ (brain) solvent concentrations. Therefore, Sprague-Dawley rats trained to lever-press for evaporated milk on a variable interval 30-s reinforcement schedule were placed in an operant test cage and exposed to clean air for 20 min, followed by a single concentration of TRI vapor (500-5000 ppm) for 100 min. Additional rats were exposed to equivalent TRI concentrations for 10, 20, 40, 60, 80, or 100 min to determine blood and brain concentration vs. time profiles. Inhalation of 1000 ppm slightly increased operant response rates, whereas 2000, 3500, and 5000 ppm decreased operant response rates in a concentration- and time-dependent manner. Accumulation of TRI in blood and brain was rapid and concentration dependent, with the brain concentration roughly twice that of blood. Plots of blood and brain TRI concentrations against operant performance showed responding in excess of control rates at low concentrations, and decreasing response rates as concentrations increased. Linear regression analyses indicated that blood and brain concentrations, as well as measures of time integrals of internal dose, were strongly correlated with operant performance. Neurobehavioral toxicity in laboratory animals, as measured by changes in operant performance, can therefore be quantitatively related to internal measures of TRI exposure to enhance its predictive value for human risk assessment.

Animals↗

Regional differentiation of the sea urchin sperm plasma membrane.

In order to study the molecular basis for the functional localization and behavioral control of sperm, we have partially characterized plasma membranes prepared from isolated head and tail fractions. These membranes have similar amounts of the Na+ pump (as reflected by (Na+,K+)-ATPase activity), whereas they differ in protein composition, binding sites for Ca2+ channel antagonists, and in the localization of enzymes of cyclic nucleotide metabolism. The Ca2+ channel antagonist D600 (and related phenylalkylamines) binds to plasma membrane preparations from sperm heads and tails with much higher affinity than do the dihydropyridine antagonists. This binding is inhibited greatly by certain monovalent (but not divalent) ions, especially Na+, Tris+, glycine ethyl ester+, and methylamine+.K+,Li+, and choline+ are less effective. In media of ionic composition resembling seawater, sperm tail membranes exhibit 6.5-fold more binding sites for D600 than do membranes from sperm head. cGMP phosphodiesterase and adenylate cyclase are also enriched in plasma membranes from the tail. Thus, the highly polarized sperm cell exhibits a regional differentiation of plasma membrane proteins implicated in behavioral control.

Animals↗

Corticotropin-releasing hormone in the lateral parabrachial nucleus inhibits sodium appetite in rats.

The present study investigated the role of corticotropin-releasing hormone (CRH) in the lateral parabrachial nucleus (LPBN) in the behavioral control of body fluid homeostasis by determining the effect of bilateral injections of the CRH receptor antagonist, alpha-helical corticotropin-releasing factor (CRF)(9-41), and the CRH receptor agonist, CRH, on sodium chloride (salt appetite) and water (thirst) intake. Groups of adult, male Sprague-Dawley rats had stainless-steel cannulas implanted bilaterally into the LPBN and were sodium depleted or water deprived. Bilateral injections of alpha-helical CRF(9-41) into the LPBN significantly potentiated water and salt intake in the sodium-depleted rats when access to fluids was restored. Bilateral injections of alpha-helical CRF(9-41) into the LPBN (1.0 microg) also increased sodium appetite in water-deprived rats. Conversely, in sodium-depleted animals, bilateral injections of CRH inhibited sodium chloride intake. These results suggest that there is an endogenous CRH inhibitory mechanism operating in the LPBN to modulate the intake of sodium (salt appetite). This mechanism may contribute to the behavioral control of restoration of body fluid homeostasis in sodium-deficient states.

Animals↗

Parallel systems of error processing in the brain.

Major neurophysiological principles of performance monitoring are not precisely known. It is a current debate in cognitive neuroscience if an error-detection neural system is involved in behavioral control and adaptation. Such a system should generate error-specific signals, but their existence is questioned by observations that correct and incorrect reactions may elicit similar neuroelectric potentials. A new approach based on a time-frequency decomposition of event-related brain potentials was applied to extract covert sub-components from the classical error-related negativity (Ne) and correct-response-related negativity (Nc) in humans. A unique error-specific sub-component from the delta (1.5-3.5 Hz) frequency band was revealed only for Ne, which was associated with error detection at the level of overall performance monitoring. A sub-component from the theta frequency band (4-8 Hz) was associated with motor response execution, but this sub-component also differentiated error from correct reactions indicating error detection at the level of movement monitoring. It is demonstrated that error-specific signals do exist in the brain. More importantly, error detection may occur in multiple functional systems operating in parallel at different levels of behavioral control.

Adult↗

Reinforcing effects of contingently administered subcutaneous injections of etonitazene in rats.

RATIONALE: Response-contingent injections of opioids have been shown to control behavior in various species. OBJECTIVE: To determine whether s.c. injections of etonitazene (ETZ) could maintain behavior in rats when administered under a single fixed-interval schedule. METHODS: Rats were trained to lever press for eight 45-mg food pellets under a single fixed-interval (FI) 10-min schedule of reinforcement: following passage of the 10-min interval, each lever press resulted in a pellet delivery until eight pellets were obtained. Delivery of the reinforcer was signaled by a change in visual stimulus conditions. Once stable responding for the food pellets under the FI 10-min schedule was established, a s.c. injection of 3.2 micrograms/kg ETZ was administered to the rat by the investigator following schedule completion and delivery of the food pellets. After receiving the drug injection, rats were returned to the experimental chamber for 30 min and exposed to the same stimulus conditions that accompanied food reinforcement. Across sessions, the number of food pellets was decreased until rats were responding solely for the drug. RESULTS: Responding for the s.c. administered drug stabilized and persisted across sessions. When saline vehicle injections were substituted for the drug injections, responses diminished across sessions to levels below that of the drug baseline. Subsequent alternating blocks of ETZ and vehicle injections produced respective increases and decreases in responding. CONCLUSION: This study demonstrates that response-contingent s.c. injections of a drug can control behavior in rats, systematically replicating a previous experiment that used the i.p. route. Since all pertinent operant behavior is emitted prior to the administration of drug, this procedure can be used for testing the reinforcing effects of a drug without interference from any direct (rate-altering) drug effects. The present findings also extend the conditions under which drugs of abuse may reinforce behavior.

Animals↗

Gender differences in risk behaviors associated with forced or pressured sex.

OBJECTIVE: To determine whether gender-specific patterns of risk behaviors are associated with a self-reported history of ever having been forced or pressured to have sexual intercourse among sexually active adolescents. SUBJECTS AND METHODS: In 1995, 21,297 eighth- through 12th-grade students in 79 public and private schools in Vermont were anonymously surveyed. Data were analyzed for 7884 sexually active students (3931 girls and 3953 boys). Demographic variables and indicators of violence, suicide, recent substance use, sexual behavior, pregnancy, and weight control behavior were assessed. Data were analyzed with multiple logistic regression. RESULTS: Of the sexually active students, 30.3% of the girls and 9.9% of the boys reported ever being forced or pressured to have sexual intercourse. Among sexually active girls, being in 1 or more physical fights in the past year (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.40-1.94), seriously considering suicide (OR, 1.97; CI, 1.69-2.31), more years of sexual activity (OR, 1.52; CI, 1.43-1.61), not using a condom at last sexual intercourse (OR, 1.28; CI, 1.09-1.49), and having been pregnant more often (OR, 1.40; CI, 1.16-1.69) were associated with having been forced or pressured to have sex. For sexually active boys, seriously considering suicide (OR, 1.64; CI, 1.23-2.20), more years of sexual activity (OR, 1.21; CI, 1.12-1.31), more male partners in the past 3 months (OR, 1.30; CI, 1.14-1.48), more female partners in the past 3 months (OR, 1.09; CI, 1.01-1.18), not using a condom at last sexual intercourse (OR, 1.37; CI, 1.03-1.82), having been involved in more pregnancies (OR, 1.64; CI, 1.29-2.08), and having vomited or used laxatives (OR, 3.44; CI, 2.18-5.43) were associated with having been forced or pressured to have sex. CONCLUSIONS: Patterns of risk behaviors differed among sexually active male and female adolescents reporting being forced or pressured to have sex. Having been forced or pressured to have sex was associated with externalizing behavior, such as fighting, among girls and with internalizing behavior, such as bulimia, among boys. These unexpected associations have notable implications for screening adolescents for a history of having been forced or pressured to have sex.

Adolescent↗

Comparison of 60-Hz electric fields and incandescent light as aversive stimuli controlling the behavior of rats.

Rats were exposed to two procedures which enabled them to press a lever to turn off a 90 or 100 kV/m 60-Hz electric field or, later in the study, illumination from an incandescent lamp. Under one procedure, a response turned off the stimulus for a fixed duration, after which the stimulus was turned on again. A response during the off-period restarted the fixed duration. None of the rats turned the field off reliably. Next, under an alternative procedure, pressing one lever turned the field off; pressing the other lever turned it back on; responding under those conditions differed little from that seen at 0 kV/m. Under both procedures, when illumination from an incandescent lamp served as the stimulus, each rat did turn the stimulus off, and performances varied with stimulus intensity. The results show that a 100 kV/m 60-Hz electric field is not sufficient to function as an aversive stimulus under two procedures where illumination from a lamp does function as an aversive stimulus.

Animals↗