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PubMed2004

Enhanced dizocilpine efficacy in heterozygous reeler mice relates to GABA turnover downregulation.

Reelin synthesized by cortical GABAergic interneurons throughout the telencephalon is secreted into the extracellular matrix (ECM) and binds with nM affinity to integrin receptors located at dendritic spine postsynaptic densities and positively modulates Arc and other dendritic resident mRNAs translation, thereby facilitating the onset of synaptic plasticity and LTP consolidation. Accordingly, the reelin haploinsufficient heterozygous reeler mice (HRM) express a marked decrease of cortical thickness, of cortical and hippocampal dendritic spine density, and of cortical GAD67 expression. Behaviorally, HRM manifest a sensorimotor deficit, an exaggerated response to fear, and a deficit in olfactory discrimination learning. HRM and wild-type mice (WTM) were trained to retrieve to criterion palatable chocolate-flavored food pellets in an eight-arm radial maze. In 9-14 days of training HRM and WTM learned the task equally well committing only a few errors. However, HRM, when compared with WTM, show a greater cognitive impairment following the administration of dizocilpine. Also, HRM are more susceptible to the increased locomotion and stereotypic behavior elicited by dizolcipine. The enhanced dizocilpine susceptibility of HRM is not due to differences in pharmacokinetics because the levels of dizocilpine in cortices of HRM and WTM were virtually equal. We also failed to detect differences between HRM and WTM in glutamate brain content and in the rate of 13C-glucose incorporation into the glutamate brain pools. In contrast we found that the conversion index of glutamate into GABA (an indirect measurement of GABA turnover rate) is decreased in cortex, hippocampus and striatum of HRM when compared to WTM. Thus, HRM recapitulate several neurochemical and behavioral endophenotypes reminiscent of schizophrenia and these mice can be proposed as a relevant animal model for the study of pharmacological treatments aimed at alleviating the sensory-motor and cognitive dysregulation associated with schizophrenia.

Animals↗

PubMed2001

Behavioral sensitization to heroin by cannabinoid pretreatment in the rat.

The behavioral consequences of acute heroin challenge (0.5 mg/kg, s.c.) were measured in rats previously submitted to repeated administration of increasing doses of the synthetic cannabinoid receptor agonist, R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55212.2) (first day 2 mg/kg, second day 4 mg/kg, third day 8 mg/kg) or vehicle. Heroin administration to rats pretreated with vehicle produced catalepsy. The same dose of heroin in WIN55212.2-pretreated rats was followed by a marked increase of locomotor activity with stereotyped and non-stereotyped behaviors. These effects were blocked by the opioid receptor antagonist, naloxone. These findings indicate that pretreatment with WIN55212.2 produces cross-sensitization to heroin in the rat. These changes might reflect long-lasting changes of receptor population or transcriptional mechanisms in the mesolimbic system.

Analgesics↗

PubMed1990

The spontaneously hypertensive rat as an animal model of attention-deficit hyperactivity disorder: effects of methylphenidate on exploratory behavior.

Spontaneously hypertensive rats (SHR) show a pervasive hyperactivity in several paradigms. Thus, these rats may be used as an animal model of childhood hyperactivity also called Attention-Deficit Hyperactivity Disorder. This disorder is frequently treated with psychomotor stimulant drugs, but little is known about the effects of such drugs on behavior. The present study investigated the behavioral effects of 1-24 mg/kg methylphenidate (Ritalin) on the exploratory behavior of male SHR and Wistar-Kyoto control rats (WKY) in a two-compartment free-exploration open field. Except following very high doses. SHR spent most of the session time in the field while WKY stayed in the home cage. Low and medium doses were followed by increased activity in the field for SHR and increased activity in the cage for WKY. The response-stimulatory effects of low to medium doses of methylphenidate are less in SHR than in WKY. Starting at medium doses, activity decreased and stereotyped behavior increased progressively by increasing dose. Locomotor activity in the field decreased following lower doses than locomotor activity in the cage, and vertical activity (rearing) was reduced by lower doses than horizontal activity (crossing). The following conclusions were drawn. (i) There is no "paradoxical" inhibition of SHR hyperactivity following methylphenidate. On the contrary, SHR activity is in fact stimulated, albeit to a lesser degree than that of WKY. (ii) The stimulatory effects of low to medium doses are, in general, most pronounced for the kind of exploratory behavior most frequently used by the rat during baseline conditions. (iii) Rearing might be more susceptible to adverse effects of methylphenidate than ambulation.

Animals↗

PubMed2005

Cocaine-induced sex differences in D1 receptor activation and binding levels after acute cocaine administration.

Although it is established that female rats have a more robust behavioral response to acute cocaine administration than male rats, the neurobiological mechanisms underlying these differences remain unclear. The purpose of the present study was to determine whether dopamine (DA) receptor activation influences sex differences in cocaine-induced behaviors. A second study was performed to determine sex differences in D1/D2 receptor levels prior to and post-cocaine administration. Male and female Fischer rats were pre-treated with the D1 antagonist SCH-23390 (0.05, 0.1, and 0.25 mg/kg, i.p.), the D2 antagonist eticlopride (0.03, 0.1 mg/kg, i.p.), or vehicle (saline) 15 min before acute cocaine (20 mg/kg, i.p.) or saline administration. Cocaine-induced ambulatory and rearing activity was greater in female than male rats. Pre-treatment with SCH-23390 affected cocaine-induced ambulatory, rearing, and stereotypic activity in a sex-dependent manner; cocaine-induced ambulatory and stereotypic behavior in female rats was reduced by the lowest dose of SCH-23390. Eticlopride did not alter behavioral responses to cocaine in male or female rats. These results suggest that in both male and female rats, activation of the D1, but not the D2, receptor modulates cocaine's motor effects. There were no sex differences in baseline levels of D1, D2, and DA transporter binding in the caudate putamen (CPu) and the nucleus accumbens (NAc). Cocaine administration reduced D1 binding levels in the CPu only in male rats. Our findings suggest that the regulation of striatal D1 binding levels after acute cocaine administration is a sexually dimorphic process. We also hypothesize that the greater sensitivity to D1 receptor blockade in female rats, as compared to male rats, may contribute to their overall increased hyperactivity in response to acute cocaine. Taken together, the D1 receptor may be an important substrate in the regulation of sex differences to cocaine-induced locomotor activity.

Animals↗

PubMedDate not supplied

Maternal behavior is impaired by methamphetamine administered during pre-mating, gestation and lactation.

Previous studies demonstrated that stimulant drugs, such as cocaine or amphetamine, administered during gestation or lactation may attenuate maternal behavior in rats. The effect of methamphetamine (MA), a drug whose usage has increased lately, on maternal behavior has not yet been investigated. The present study tested the effect of MA (5 mg/kg daily) administered prior to, during and after gestation on maternal behavior. Regularity of the estrous cycle, the incidence of impregnation, and the weight gain was compared between groups (control, saline- and MA-treated). Maternal behavior was examined using two tests: Observation test (without disturbance of the mother and pups) and Retrieval test (with short separation of pups from the mother). All tests were conducted prior to dosing each day. In the Observation test, MA decreased the blanket position of active nursing, while increasing passive nursing. There were no MA-induced changes in other maternal activities such as mother being in the nest, in contact with pups, or grooming pups. MA increased some non-maternal activities, such as drinking, eating, and sleeping, while decreasing stereotypic behavior (sniffing and rearing) when compared to controls. In the Retrieval test, MA-treated mothers were slower in retrieving the first pup, returning the first pup into the nest, and returning all pups into the nest. Interestingly, there were differences in maternal behavior also in saline-treated mothers relative to controls. Saline-treated mothers spent more time in the nest and groomed pups more than controls or MA-treated mothers. In conclusion, the present study demonstrates a novel finding that MA administered during pre-mating, gestational and lactational periods has a negative effect on maternal behavior toward pups.

Animals↗

PubMed2003

Entorhinal inputs to dentate gyrus are activated mainly by conditioned events with long time intervals.

Brain mechanisms of mammalian learning and memory have long been associated with the hippocampus. Although the role of the hippocampus in spatial behavior is well established, there is no general consensus on the function of the hippocampus in nonspatial tasks. Task-related changes in evoked potentials were first reported by Deadwyler and colleagues in the dentate gyrus, with a peak at 100 ms in rats trained in an auditory discrimination task (Deadwyler et al., Brain Res 161:211-225, 1979). Surprisingly, these results have not been confirmed by other investigators. In the present report, we set out to assess the task parameters that induce, modulate, and suppress this potential. Using multielectrode probes and current source density analysis, we monitored the entorhinal input to the dentate gyrus in behaving rats. Both differential and simple auditory conditioning led to the appearance of a large negative potential at 100 ms in the perforant path zone of the dentate gyrus. This negativity was found in averaged and in single-trial, evoked potentials. Current source density analysis revealed sinks in the perforant path zone of the molecular layer of the dentate gyrus with corresponding sources in the hilus. Once trained for differential conditioning, decrements of target probability consistently increased the amplitude of this negativity. When using a single-tone, stimulus-response task, the negative potential occurred with long (70-s), but not with short (10-s) intertrial intervals. Appearance of the potential coincided with a switch in response strategy and disappeared under stereotypical behavior. These data are best explained under the assumption that long intertrial intervals lead to transitions in task-related reference frames enabling a switch to more appropriate response strategies. Such transitions are not required during short interval stereotyped performance.

Acoustic Stimulation↗

PubMed1992

An LH-RH antagonist inhibits the behavioral effects of the agonist D-TRP-6-LH-RH in mice.

The effects of a potent LH-RH receptor antagonist, [Ac-4-Cl-D-Phe1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH (ORG 30276), on the behavioral actions of the LH-RH agonist, D-Trp-6-LH-RH, were studied in mice. The subcutaneous (SC) administration of 100 micrograms/kg D-Trp-6-LH-RH inhibited ambulation in an open-field, produced analgesia in the hot-plate and tail-flick tests. These effects of the agonist were totally antagonized by pretreatment with ORG 30276 at a dose of 100 micrograms/kg SC. In the apomorphine-induced cage-climbing test, both the agonist and the antagonist alone or together suppressed the duration of stereotyped behavior in dose-dependent manner, but, as there was no additive synergism after combined treatments, it seems that the two substances mutually diminish each other's effects. The results indicate that the behavioral effects of the LH-RH agonist can be antagonized by pretreatments with a potent LH-RH antagonist designed to block pituitary LH-RH receptors, with the exception of the suppression of apomorphine-induced cage-climbing, where special type of receptors and/or mechanisms might be involved.

Analgesia↗

PubMed1992

Sensitivity and specificity of the Behavioral Summarized Evaluation (BSE) for the assessment of autistic behaviors.

The Behavior Summarized Evaluation (BSE), developed for the assessment of autistic behavior, was specifically designed to evaluate the severity of behavioral problems in autistic children involved in bioclinical and therapeutic studies. The reliability studies and the factorial analysis of this scale have been previously published. The present paper examines the effectiveness of the BSE to discriminate 58 autistic from 58 nonautistic mentally retarded children. The BSE clearly separated the two samples of children. A most efficient combination of 8 items emerged from the stepwise item selection procedure. The between-group differences were highest on 4 items, indicating that the most particular pattern in autistic compared to nonautistic children could be the association of autistic withdrawal and stereotypic behaviors. Our findings suggest that the BSE could help in the detection and evaluation of autistic developmental deviance. Implications for further research are discussed.

Autistic Disorder↗

PubMed1992

Sodium arsanilate-induced vestibular dysfunction in meadow voles (Microtus pennsylvanicus): effects on posture, spontaneous locomotor activity and swimming behavior.

Vestibular dysfunction was chemically induced in male meadow voles (Microtus pennsylvanicus) by intratympanic injections (30 mg per side) of sodium arsanilate (atoxyl). The control group received intratympanic injections of isotonic saline. After a one-week recovery period the voles were behaviorally assayed for integrity of their labyrinthine systems. All subjects were tested for the presence of the air-righting reflex and body rotation-induced nystagmus. Three weeks later a multivariate assessment of spontaneous motor activity of the voles was carried out in the automated Digiscan Activity Monitor. In addition, the swimming behavior of the voles was examined. Voles with vestibular dysfunction exhibited pronounced postural abnormalities (head dorsiflexion), were not able to swim with their nose above the water for a 1 min test period, and displayed disorientation and thrashing movements. In the Digiscan activity test the atoxyl-treated voles displayed significantly more activity in the horizontal measures (Ps less than 0.01), including greater distance travelled per movement and greater speed of movements, relative to the control animals. The labyrinthectomized group also spent significantly (P less than 0.05) less time in vertical movements and exhibited significantly more time in stereotypic behavior (P less than 0.01), relative to controls. Atoxyl-treated voles also showed significantly less thigmotaxis (wall-hugging) than the control animals (P less than 0.01). In general, changes in spontaneous behavior observed in the sodium arsanilate-treated voles were consistent with the presence of postural and balance abnormalities and a redirecting of exploratory vertical movements toward horizontal locomotion to the extent that these animals were clearly hyperactive in this dimension. The multivariate behavioral assessment available in the Digiscan Activity Monitoring system, thus seems to be especially useful in the examination of behavioral components affected by vestibular dysfunction.

Animals↗

PubMed2000

Sustained behavioral stimulation following selective activation of group I metabotropic glutamate receptors in rat striatum.

Group I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium-sized spiny projection neurons of striatum. Activation of this group of the mGluRs modifies neuronal physiology through stimulation of phosphoinositide hydrolysis and intracellular Ca(2)+ release. Unlike the ionotropic glutamate receptors that mediate rapid synaptic transmission, activation of the mGluRs produces long-lasting actions brought about by modulation of activities of intracellular effectors. In this study, the role of the group I mGluRs in the modulation of extrapyramidal motor function was examined using a group I selective agonist, 3, 5-dihydroxyphenylglycine (DHPG), in chronically cannulated rats. Bilateral injections of DHPG at a series of subtoxic doses (20, 40, 80, and 160 nmol) into the central part of the dorsal striatum produced hyperlocomotion and a unique stereotypical behavior (spontaneous and repetitive twitching movement of the head and forepaws) in a dose-dependent manner. The characteristic twitchy behavior usually commenced 30 min to 1 h, and could last as long as 10 to 12 h, after a single injection of the group I agonist. The behavioral responses to DHPG administration were markedly antagonized by intrastriatal injection of the group I antagonist PHCCC (10 nmol), but not the group II/III antagonist MSOPPE (10 nmol). Intrastriatal administration of 20 nmol dantrolene, an inhibitor of intracellular Ca(2)+ mobilization, also prevented DHPG-stimulated motor activities. However, blockade of dopamine D(1) receptors with systemic administration of SCH-23390 (0.1 mg/kg, SC) did not alter the ability of DHPG to provoke behavioral activities. These data indicate that selective activation of the DHPG-sensitive group I mGluRs in the striatum can produce long-lasting stimulation of motor activity. DHPG-induced motor stimulation involves the mobilization of intracellular Ca(2)+ stores, but appears to be independent of D(1) dopaminergic transmission.

Animals↗

PubMed2005

Behavioral features of CHARGE syndrome (Hall-Hittner syndrome) comparison with Down syndrome, Prader-Willi syndrome, and Williams syndrome.

CHARGE syndrome, or Hall-Hitner syndrome (HHS), has been delineated as a common syndrome that includes coloboma, choanal atresia, cranial nerve dysfunction (particularly asymmetric facial palsy and neurogenic swallowing problems), characteristic ear abnormalities, deafness with hypoplasia of the cochlea and semicircular canals, genital hypoplasia, and variable heart defects, orofacial clefting, tracheo-esophageal fistula, renal anomalies, thymic/parathyroid hypoplasia, spine anomalies, short broad neck with sloping shoulders, and characteristic facial features. We conducted behavioral and personality assessments in 14 boys with HHS syndrome aged 6-21 years, and compared their characteristics with similar data from 20 age-matched boys with Down syndrome (DS), 17 boys with Prader-Willi syndrome (PWS), and 16 boys with Williams syndrome (WS). We used the Reiss Profile of Fundamental Goals and Motivation Sensitivities, the Achenbach Child Behavior Checklist (CBCL), and the Aberrant Behavior Checklist (ABC). All 14 boys with HHS were legally deaf, and 10 of the 14 were also legally blind. In comparison these other syndromes, boys with HHS had behavior that resembled autistic spectrum disorder. They were socially withdrawn, lacked interest in social contact, and manifested reduced seeking of attention from others, with hyperactivity and a need to maintain order. Though the boys with HHS showed decreased social interaction, they were not as socially impaired as in classic autism. Their language was delayed due to dual sensory impairment, cranial nerve deficits, and chronic medical problems, but their language style was not abnormal (no echolalia or jargon, no scripted phrases, and no pronoun reversal). Boys with HSS appeared frustrated, but they were not aggressive, or at risk for delinquency, manifesting few stereotypic behaviors or unusual preoccupations. They did not have a restricted repertoire of activities and interests. Their behavioral features appeared to be due to dual sensory impairment affecting hearing and vision, rather than to primary autistic spectrum disorder, but successful remediation requires similar educational interventions, which are discussed herein.

Abnormalities, Multiple↗

PubMed1996

L-deprenyl (selegiline) exerts anticonvulsant effects against different seizure types in mice.

L-Deprenyl (selegiline), a selective inhibitor of monoamine oxidase type B, has recently been shown to exert anticonvulsant and antiepileptogenic effects in the kindling model of partial (focal) epilepsy. In the present study, we examined if L-deprenyl exerts anticonvulsant effects in standard rodent models of generalized seizures. In addition to anticonvulsant activity, behavioral effects induced by L-deprenyl were monitored closely. To assess the stereoselectivity of anticonvulsant and behavioral effects of deprenyl, the D-enantiomer was included in the studies. Furthermore, the antiepileptic drug phenobarbital was used for comparison. The following tests were performed in mice: 1) the threshold for tonic electroconvulsions; 2) the maximal electroshock seizure test with fixed supramaximal (suprathreshold) stimulation; 3) the threshold for myoclonic, clonic and tonic seizures in response to i.v. infusion of pentylenetetrazole (PTZ); 4) the s.c. PTZ seizure test, with a fixed dose of PTZ (80 microgram/kg) for seizure induction; 5) the rotarod and chimney tests for determination of motor impairment. Furthermore, animals were observed in cage and open field for stereotyped behavior and other behavioral abnormalities. L-Deprenyl, tested at doses of 1 to 40 microgram/kg i.p., significantly increased myoclonic and clonic PTZ thresholds and the threshold for tonic electroconvulsions, whereas D-deprenyl was either ineffective or exhibited a lower anticonvulsant potency than L-deprenyl. Both drugs were ineffective in the maximal electroshock seizure and s.c. PTZ seizure tests. In contrast to the higher anticonvulsant potency of L-deprenyl in seizure threshold tests, D-deprenyl was more potent than L-deprenyl to induce behavioral abnormalities, such as hyperlocomotion. The data indicate that L-deprenyl exerts anticonvulsant activity against different seizure types. This anticonvulsant activity and the previously reported neuroprotective and cognition-enhancing action of L-deprenyl offer a unique combination of drug effects which might be of clinical benefit in patients with epilepsy.

Animals↗

PubMed1994

Ontogeny of enhanced striatal dopamine release in rats with methamphetamine-induced behavioral sensitization.

The behavioral sensitization has not been observed in rats under three weeks of age when administration of repeated psychostimulants is started. The aim of our study was to determine the effect of methamphetamine (MAP)-induced behavioral sensitization ontogeny on MAP challenge-induced changes of striatal extracellular concentrations of dopamine (DA) and its metabolites, using in vivo microdialysis. Experimental rats aged 7, 14, 21, 28, and 56 postnatal days (PNDs) were injected IP twice daily with 2 mg/kg MAP for three days, followed by 4 mg/kg for three days. Matched control rats were given equivalent volumes of saline according to the same schedule. Dialysis experiments were carried out 21 days after the last MAP or saline injection. All the rats were injected (IP) with a challenge dose of MAP (4 mg/kg). We reconfirmed that MAP-induced stereotyped behavior was enhanced significantly only when MAP pretreatment was started on PNDs 21, 28, and 56, but not PNDs 7 and 14. Correspondingly, the MAP challenge induced significantly greater increases in striatal extracellular DA concentrations in the MAP-pretreated rats compared with control rats only when MAP pretreatment was initiated on PNDs 21, 28, and 56, but not in younger rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: interactions with amphetamine.

To investigate behavioral and neurochemical effects of neurotrophic factors in vivo, rats received continuous 14 d infusions of either brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or vehicle unilaterally into the substantia nigra. BDNF and NT-3 decreased body weights, an effect that was sustained over the infusion period. BDNF elevated daytime and nocturnal locomotion compared with infusions of vehicle or NT-3. At 2 weeks, a systemic injection of amphetamine (1.5 mg/kg, s.c.) increased the frequencies and durations of rotations contraversive to the side of BDNF and NT-3 infusions. Both factors attenuated amphetamine-induced locomotion without affecting amphetamine-induced stereotyped behaviors such as sniffing, head movements, and snout contact with cage surfaces. Only BDNF induced backward walking, and this response was augmented by amphetamine. BDNF, but not NT-3, increased dopamine turnover in the striatum ipsilateral to the infusion relative to the contralateral striatum. Both trophic factors decreased dopamine turnover in the infused substantia nigra relative to the contralateral hemisphere and increased 5-HT turnover in the striatum of both sides. Contraversive rotations were positively correlated with dopamine content decreases and 5-HT turnover increases in the striatum ipsilateral to the infused substantia nigra. Backward walking was positively correlated with increased dopamine and 5-HT turnover in the striatum of the infused hemisphere. Supranigral infusions of BDNF and NT-3 alter circadian rhythms, spontaneous motor activity, body weights, and amphetamine-induced behaviors including locomotion and contraversive rotations. These behavioral effects of the neurotrophins are consistent with a concomitant activation of dopamine and 5-HT systems in vivo.

Amphetamine↗

PubMed2002

Acute cocaine differentially alters accumbens and striatal dopamine clearance in low and high cocaine locomotor responders: behavioral and electrochemical recordings in freely moving rats.

Behavioral responses of rodents to cocaine are characterized by marked individual variability. Here, outbred male Sprague-Dawley rats were profiled based on concomitant recording of behavioral and electrochemical responses. Rats were categorized as either low or high cocaine responders (LCRs or HCRs, respectively) based on their differential locomotor responsiveness to an acute, low-dose injection of cocaine (10 mg/kg i.p.). LCRs and HCRs also differed in other cocaine-induced behaviors. The role of the dopamine transporter (DAT) in mediating the behavioral differences in cocaine responsiveness in LCRs and HCRs was investigated by high-speed chronoamperometric recording of exogenous dopamine (DA) clearance signals in nucleus accumbens (NAc) and dorsal striatum (dSTR). Higher volumes of DA were required in NAc of HCRs, than of LCRs, to produce equivalent peak DA signal amplitude (A(max)) responses. In HCRs, systemic cocaine administration evoked an immediate and prolonged 2-fold augmentation in A(max) in both brain regions, coincident with locomotor activation. The cocaine-induced decrease in the efficiency of DA clearance (k) in NAc of HCRs was more immediate and prolonged than in dSTR, where the transient decrease coincided with maximal stereotypic behavior. In contrast, in LCRs, A(max) was not altered by cocaine, and decay rate constant (k) was transiently attenuated only in dSTR. Correlation analyses of individual responses revealed that cocaine-induced changes in DA clearance signal parameters accounted for 20 to 40% of the variation in behavioral responsiveness to cocaine. Overall, our findings emphasize the importance of characterizing individual responses to understand more fully the range of functional consequences resulting from DAT inhibition.

Algorithms↗

PubMed2000

Behavioral activating effects of adrafinil in aged canines.

Adrafinil, a vigilance enhancing pharmaceutical, was administered to aged dogs for 14 consecutive days at doses of 10, 20, 30, or 40 mg/kg using a crossover design. The effects on spontaneous behavior in a 10-min canine open-field test were systematically recorded every fourth day, starting with day 1 of treatment. The open field tests were given 2 or 10 h following oral administration of capsules containing either adrafinil or lactose, the placebo control. Adrafinil caused an increase in locomotor activity at the three highest doses at both the 2- and 10-h intervals and during both the first (days 1 and 5) and second treatment week (days 9 and 13). Adrafinil also caused a transient increase in directed sniffing. At the highest dose level, adrafinil caused a decrease in urination frequency. The increased locomotion was generally unaccompanied by stereotypical behavior in the test session. There was some variability; a subpopulation of animals showed either no effect, or decreased locomotion. The individual differences were correlated with changes in serum levels of adrafinil 10 h following treatment.

Aging↗

PubMed2005

[New therapeutic strategies for behavioral and psychological symptoms of dementia].

Interventional studies, with the aim of reducing the burden of care through drug or non-drug therapies of behavioral and psychological symptoms of dementia (BPSD), have been scarce. However, we are now able to do pharmacological management for BPSD with new drugs such as atypical neuroleptics, SSRIs, and cholinesterase inhibitors. Delusions of theft are one of the most frequently observed BPSD in patients with AD. In addition, the delusions and ensuing aggression and anxiety are major factors that increase the burden of caregivers. Delusions of theft in patients with AD were eliminated or reduced with low-dose atypical neuroleptics (risperidone). This significantly reduced the burden of care overall for caregivers. New therapeutic strategies such as cholinesterase inhibitors for visual hallucinations in DLB and SSRIs for overeating and stereotyped behavior in FTLD might also remarkably reduce the burden of care for these patients. For many dementia patients, there are still no drugs that offer a principal cure. It is, therefore, important to evaluate their BPSD correctly at the earliest possible time, so that the burden of caring can be reduced through appropriate drug treatment. This reduction is critical for the continuation of satisfactory at-home care and might contribute to the health economics.

Alzheimer Disease↗

PubMed1992

Dopaminergic stimulation of oxytocin concentrations in the plasma of male and female monkeys by apomorphine and a D2 receptor agonist.

Administration of the dopamine receptor agonist apomorphine causes a dose-dependent increase in plasma oxytocin concentrations and dose-specific behavioral changes in rodents. To investigate whether dopamine receptor agonists will elicit similar neuroendocrine and behavioral effects in primates, we administered graded doses of apomorphine and the respective dopamine D1 and D2 receptor agonists, CY 208-243 and LY 163502, to monkeys and monitored plasma concentrations of oxytocin and behavior. Five female rhesus, two male rhesus, and two male cynomolgus monkeys had chronic indwelling venous catheters implanted and were maintained on standard jacket/tether/swivel systems to allow remote blood sample collection. During experiments, blood samples were collected 10 and 5 min before drug injection and at 2- to 120-min intervals after each injection. Apomorphine (50-400 micrograms/kg) and LY 163502 (10-100 micrograms/kg) elicited dose-dependent stimulations of oxytocin secretion. CY 208-243 (100-400 micrograms/kg) did not significantly affect oxytocin secretion. Low doses of apomorphine (50-100 micrograms/kg) and LY 163502 (10-25 micrograms/kg) elicited yawning, and high doses of apomorphine (200-400 micrograms/kg) and LY 163502 (50-100 micrograms/kg) elicited stereotypic behaviors. No behavioral effects of CY 208-243 (100-400 micrograms/kg) were observed. The magnitude of the oxytocin secretory responses varied among animals, but was similar in male and female monkeys. In summary, apomorphine and LY 163502 both elicited dose-related stimulation of oxytocin secretion coupled with dose-specific behavioral changes in male and female monkeys, while no effects of CY 208-243 on these parameters were observed. We conclude that dopamine receptor agonists, and in particular D2 agonists, may be useful tools for studies exploring the physiological and behavioral actions of oxytocin in primates.

Animals↗