Behavioral and Neurochemical Effects of Fencamfamine on Rats: A Chronobiologic Approach

Fencamfamine (FCF) is a psychostimulant classified as an indirect dopaminergic agonist. Circadian rhythms of some behavioral and neurochemical parameters were investigated in control rats and in rats which had been treated with a single dose of FCF across the 24-hr span. Rats were entrained to light/dark (LD) 12:12, lights on from 0700 to 1900. In behavioral experiments (performed in March) the rats were injected intraperitoneally with saline or FCF (3.5 mg/kg) at one of six times: 0900, 1300, 1700, 2100, 0100 or 0500. Fifteen minutes after treatment the duration of sniffing, rearing and locomotion was recorded during 120 min. Controls showed circadian rhythms for sniffing and rearing with acrophases at 2255 and 0118, respectively. In animals treated with FCF, only locomotion displayed significant circadian variation with acrophase at 1912. Two-way analysis of variance (ANOVA) showed a statistically significant circadian time-dependent effect of FCF on all behavioral parameters studied; the increase of sniffing, rearing and locomotion induced by FCF was higher in rats treated during the rest phase. In the biochemical studies (performed between March-June), rats were treated (i.p.) with saline or FCF (10 mg/kg) at one of four times: 0900, 1700, 2100 or 0100. The levels of homovanillic acid (HVA) in the striatum and tuberculum olfactorium, 5-hydroxyindolacetic acid (5-HIAA) in the cerebellum and 3-methoxy-4-hydroxypheniglycol (MHPG) in the frontal cortex were determined. Controls showed circadian rhythms for HVA (striatum), MHPG (frontal cortex) and 5-HIAA (cerebellum) with acrophases at 2233, 1955 and 1029, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antagonism of AP-5-induced sniffing stereotypy links umespirone to atypical antipsychotics.

Blockade of glutamatergic transmission in the striatum (using the NMDA-antagonist DL-2-amino-5-phosphonovaleric acid AP-5) was recently shown to induce stereotyped sniffing in rats. Comparable stereotyped behaviour is well known to be elicited by stimulation of dopamine activity, which since long was the basis for experimental models to check for possible antipsychotic activity of new compounds. However, whereas dopamine-induced stereotypies are antagonized only by classical neuroleptics, stereotypies induced by blockade of glutamatergic transmission are antagonized by classical as well as by atypical antipsychotics. Umespirone, a novel psychotropic which has been reported to exhibit behavioural effects predictive for antipsychotic as well as anxiolytic potential was evaluated for antagonistic effects against AP-5-induced behaviour. The profile of umespirone was compared with the profile of a non-benzodiazepine anxiolytic buspirone as well as with previously published data of neuroleptics. Umespirone like clozapine specifically antagonized AP-5-induced sniffing, i.e. did not impair spontaneous sniffing but reversed AP-5-induced excessive sniffing. In contrast, buspirone impaired spontaneous and AP-5-induced sniffing to about the same extend. These results are in accordance with the glutamate hypothesis of schizophrenia and again give evidence that umespirone should have antipsychotic potential and a very low liability to exhibit unspecific sedative action.     

Dose-response effects of orexin-A on food intake and the behavioural satiety sequence in rats

Although intracerebroventricular (i.c.v.) administration of orexin-A has been reported to stimulate food intake and/or feeding behaviour in rats, mice and goldfish, little attention has thus far been paid to its effects on normal patterns of feeding. In the present study, a continuous monitoring technique was used to characterise the effects of this novel neuropeptide on the microstructure of rat behaviour during a 1-h test with palatable wet mash. Particular attention was devoted to the behavioural satiety sequence, in which feeding is followed by grooming and resting. Although results confirmed the hyperphagic effects of orexin-A (3.33-30.0 microg i.c. v.), gross behavioural analysis failed to reveal any reliable effects of peptide treatment on eating, drinking, sniffing, grooming, resting, locomotion or rearing. However, microstructural analysis revealed behavioural effects of orexin-A that are both dose- and time-dependent. At lower doses (3.33-10.0 microg), orexin-A primarily delayed behavioural satiety, i.e. the normal transition from eating to resting. In contrast, the 30 microg dose initially induced a sedative-like effect, significantly suppressing eating and other active behaviours for the first 15-20 min of the test period. This sedative-like effect resulted in a phase-shifting of the entire behavioural sequence with higher than control levels of eating, grooming, locomotion, rearing and sniffing observed over the second half of the test session. Present findings illustrate the advantages of microstructural behavioural analysis and suggest that the hyperphagic response to low doses of orexin-A results largely from a delay in behavioural satiety while that seen in response to high doses may occur in rebound to initial behavioural suppression. Further studies will be required to confirm the identity of the specific orexin receptors (i.e. OX(1) or OX(2)) involved in mediating the dose-dependent behavioural effects reported.     

The role of striatal glutamate receptors in models of Parkinson's disease

Summary The aim of the study was to examine the effect of antagonists of the NMDA receptor on the parkinsonian-like muscle rigidity in rats. Reserpine and haloperidol increased the muscle resistance of the hind foot to passive movements, as well as the reflex electromyographic (EMG) activity in the gastrocnemius and tibialis anterior muscles. MK-801 (0.32-1.28 mg/kg sc), an uncompetitive antagonist of the NMDA receptor, and L-701,324 (5-40 mg/ kg ip), an antagonist of the glycine site, reduced the muscle tone and the reflex EMG activity enhanced by reserpine or haloperidol. AP-5 (2 and 5 ,g/ 0.5 pl), a competitive antagonist of the NMDA receptor, and 5,7-dichlorokynurenic acid (1.0-4.5g/0.5 pl), the glycine site antagonist injected bilaterally into the rostral striatum, inhibited the muscle rigidity induced by haloperidol. In contrast, AP-5, injected alone bilaterally into the intermediate-caudal striatum induced muscle rigidity. The present results suggest that: (1) the inhibitory effect of the NMDA receptor antagonists on the parkinsonian-like muscle rigidity depends, at least partly, on their action on the rostral striatum; (2) the blockade of NMDA receptors in the intermediate-caudal striatum may reduce the beneficial impact of these compounds.     

A study on specific behavioral effects of formaldehyde in the rat

It has been reported that single exposure of rats of low-level formaldehyde vapor concentrations causes significant alteration in their motor activity in the inhalation chamber. In this study, we determined the effects of formaldehyde on the locomotor activity and behavior of adult male and female Lew. 1K rats in an open field two hours after termination of a single two hours lasting inhalative exposure to approximately 0.1, 0.5, or 5 ppm. Following behavioral parameters were quantitatively examined: numbers of crossed floor squares, occurrence frequencies of air and floor sniffing, grooming, rearing, and wall climbing, as well as the incidence of fecal boli. In the open field situation, the males of all formaldehyde groups crossed significantly lower numbers of floor squares. Furthermore, significant decrease in the occurrence frequencies of floor sniffing, rearing, and wall climbing were observed. Within the female rat groups exposed to 0.5 or 5 ppm formaldehyde, a significantly decreased numbers of crossed squares were registered, while this parameter remained unchanged in the 0.1 ppm group. Other parameters were also affected by the formaldehyde inhalation (e.g. significant increase in the occurrence frequencies of air sniffing in the 0.1 and 0.5 ppm groups and significant decrease in the numbers of floor sniffing in the 0.5 and 5 ppm groups, respectively). The incidence of fecal boli was not affected in any exposure group neither in males nor in females. It is concluded from the results obtained that formaldehyde significantly affects the locomotor behavior of adult male and female rats in the open field after a single inhalative exposure to the above mentioned concentrations.     

Behavioral consequences of methyllycaconitine in mice: a model of alpha7 nicotinic acetylcholine receptor deficiency

Diminished expression of the alpha(7) nicotinic acetylcholine receptor occurs in selected brain regions of patients with schizophrenia, which may account for pathophysiological abnormalities and some of the deficits in attention and information processing. In view of this neurotransmitter receptor deficit, we wished to characterize the behavioral consequences associated with the administration of methyllycaconitine (MLA), a competitive alpha(7) nicotinic acetylcholine receptor antagonist, in mice. In this study, we injected groups of 12 outbred NIH Swiss male mice intraperitoneally with MLA (1.0, 3.2 and 10.0 mg/kg) and its saline vehicle. Thereafter, individual mice were observed over a one-hour interval and the intensity of a variety of behaviors were rated on a 4-point scale. The observed behaviors included: gnawing/chewing, rearing, grooming, sniffing, climbing, Straub tail, locomotion and ataxia. MLA produced statistically significant changes in the following observed behaviors: rearing, sniffing, climbing, and locomotion. A profile of the behavioral changes related to MLA administration in mice could lead to the development of a screening paradigm for alpha(7) nicotinic acetylcholine receptor agonist interventions. Ideally, an effective alpha(7) nicotinic acetylcholine receptor agonist intervention would target domains of psychopathology, especially cognitive symptoms that contribute to the profound functional disability that is often associated with schizophrenia.     

Antagonism of AP-5- and amphetamine-induced behaviour by timelotem as compared with clozapine and haloperidol

Bilateral intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5), that blocks glutamatergic transmission at the N-methyl-d-aspartate preferring receptor, induces sniffing and body turns and reduces grooming in rats. Timelotem, a representative of the newly developed chemical class of anellated benzodiazepines antagonized specifically AP-5-induced sniffing and body turns. Classical (haloperidol) as well as atypical (clozapine) neuroleptics had recently been shown to antagonize AP-5-induced sniffing; clozapine, like timelotem, but not haloperidol, additionally antagonized AP-5-induced body turns. Further, timelotem antagonized amphetamine-induced stereotyped behaviour in rats, but was found less active than haloperidol in this test. Comparing the activity of drugs in both paradigms revealed that haloperidol inhibited AP-5-induced sniffing and amphetamine-induced stereotypies within the same dose range, but timelotem and clozapine were found more potent in the AP-5 test than in the amphetamine test. Thus, detailed drug profiles discriminate timelotem and clozapine from haloperidol, linking timelotem again to atypical antipsychotic compounds.     

Neurotransmission of autonomic components of aortic baroreceptor afferents in the NTS of awake rats

The effect of sequential blockade of N-methyl-D-aspartic acid (NMDA) receptors with DL-2-amino-5-phosphonopentanoic acid (AP-5) and non-NMDA receptors with 6,7-dinitroquinoxaline-2,3 dione (DNQX) in the nucleus tractus solitarii (NTS) on the cardiovascular responses to electrical stimulation (ES) of the aortic depressor nerve (ADN) was evaluated in awake rats. Two protocols were used. In protocol 1, bilateral microinjection of AP-5 into the NTS (n = 7) reduced the hypotensive response to ES of the ADN; subsequent microinjection of DNQX produced additional reduction in this response. AP-5 reduced the bradycardic response, and DNQX almost abolished this response. In protocol 2, bilateral microinjection of DNQX into the NTS (n = 6) reduced the hypotensive response, and subsequent microinjection of AP-5 significantly reduced this response. DNQX produced a significant reduction in bradycardic response, and AP-5 abolished this response. The data indicate that processing of the parasympathetic component of the NTS aortic baroreceptor afferents is mediated by both NMDA and non-NMDA receptors, whereas processing of the sympathoinhibitory component seems to be only partially mediated by ionotropic receptors.     

Concomitant D1 dopamine receptor activation (SKF 38393) unmasks D2 dopaminergic actions of B-HT 920 in mice.

The present study attempts to demonstrate D1/D2 dopamine (DA) receptor interactions during stereotyped behaviour in mice. B-HT 920 [2-amino-6-allyl-5, 6, 7, 8-tetrahydro-4H-thiazolo-(4, 5-d)-azepine] (0.05-1.0 mg/kg), a selective D2-DA agonist, induced mild per se stereotypy consisting mainly of sniffing and rearing responses. Apomorphine, a mixed D1/D2 agonist, also produced typical stereotypic response in mice. The stereotypic response of B-HT 920 was blocked by D2-DA antagonist, sulpiride (50 mg/kg). The effect of apomorphine was not influenced by co-treatment with SKF 38393. Simultaneous administration of B-HT 920 (0.1-0.5 mg/kg) with SKF 38393 (5 mg/kg), a selective D1-DA agonist, elicited dramatic increase in stereotyped behaviours in naive as well as in 24 hr reserpinised (2 mg/kg) mice. Co-treatment of apomorphine (0.5 mg/kg) with B-HT 920 (0.1, 0.25 mg/kg) also resulted in a clearly synergistic effect on stereotyped behaviour. These potentiated responses were reduced or blocked by haloperidol, a D2-DA antagonist. The data suggest that in presence of concomitant stimulation of D1-DA receptors. B-HT 920 exhibits full expression of postsynaptic D2-DA receptor mediated behavioural effects.     

Genetic evidence that cocaine and caffeine stimulate locomotion in mice via different mechanisms

The effects of cocaine and caffeine on motor activity in two mouse strains 129/OlaHsd (129) and C57BL/6J (C57) were compared. The former mice exhibited lower basal motor activity than the latter. Cocaine (3, 10, 30 mg/kg) injected i.p. in habituated C57 mice produced a dose-dependent increase in rearing, motility and locomotion. In 129 mice, little or no stimulation was seen and only with the highest dose of cocaine. In both strains caffeine (3, 15, 30 mg/kg) produced a dose-dependent increase in rearing, motility and locomotion. The effect of caffeine on rearing was greater in C57 than in 129 mice, but motility and locomotion were stimulated approximately to the same degree in both strains. Thus, differences in the sensitivity to caffeine and cocaine between mouse strains provide genetic evidence that these two stimulants probably produce locomotor stimulation via somewhat different mechanisms.     

An analysis of spontaneous behavior following acute MDMA treatment in male and female rats

3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a widely abused drug that impairs behavioral, emotional and cognitive functions in humans and animals. The aim of this study was to evaluate MDMA effects on the spontaneous behavioral repertoire of rats with a focus on the gender differences. MDMA was given subcutaneously in a single dose of 2.5, 5 and 10 mg/kg and the spontaneous behavior of male and female rats was studied using the open field test. Behavioral patterns (locomotion, rearing, floor-sniffing, air-sniffing, grooming, immobility and stereotypy) were registered in two sessions - 30 and 60 min following MDMA administration; each session lasting 5 min. We found that MDMA totally disrupted the structure and timing of spontaneous behavioral patterns in both genders; no evident differences were measured between either of the sessions. MDMA irrespective of the dosage produced hyperlocomotion, excessive floor-sniffing and almost absolute suppression of grooming and immobility. A biphasic effect of MDMA was found in rearing. Gender differences were present namely in rearing and sniffing stereotypy. This study also confirms that behavioral experiments should focus on more behavioral elements than only on e.g. locomotion and that the observer-based approach still gives the most reliable results.     

Specificity of nucleus accumbens to activities related to cholecystokinins in rats

Cholecystokinin octapeptide (CCK-8) or cholecystokinin tetrapeptide (CCK-4) were bilaterally injected into the areas where dopamine (DA) terminals and receptors have been detected; nucleus accumbens (NA), nucleus caudatus (NC), medial profrontal cortex (MPC), or prefrontal cortex (PC). The amount injected to each animal varied from 0 (control), 1 to 500 ng of CCK-8 and 0 (saline control), 0.5 to 2.5 micrograms of CCK-4 in NA in a volume of 1 microliter. The other areas received 500 ng CCK-8, 2.5 micrograms CCK-4 and proper control injections. The effects were observed in an open-field apparatus by measuring locomotor and rearing responses, the latency to move out of a specified area where the animal was first placed, and the amount of excretory bolus during a 5 min period following injections. When injected into NA, CCK-8 decreased locomotion and rearing at doses of 2.5 ng or more in a dose-related manner whereas CCK-4 increased locomotion and rearing at 1 microgram or more. The effects on latency and defecation were not detected. When the peptides were injected into NC, MPC or PC no effects were detectable. It appears that the effects of CCK-8 and CCK-4 on the exploratory responses are site-specific at NA where CCK-8 and DA are found to coexist in same neurons. CCK-4, a metabolite of CCK-8, could exert a negative feedback to moderate the effect of CCK-8.     

Behavioral effects of thyrotropin releasing hormone in frontal decorticated rats

A low dose intracerebroventricular injection of thyrotropin releasing hormone (TRH, 100 ng) changed many behavioral responses in the rat. TRH increased locomotion, scratching, body shaking, piloerection, and rearing, but decreased sniffing, and resting. Ablation of frontal neocortex further enhanced the TRH effects on locomotion and resting. A dose effect of TRH (0, 5, 10, 50, 100 ng) to increase general activity was established and the effect was further enhanced by decortication. In our test situations decortication had no effect by itself. Since the TRH effects became much more pronounced without the frontal neocortex it appears that the cortex exerts a powerful inhibitory effect to moderate the TRH effects. The TRH effect does not depend upon the frontal cortex, actually a cortical function is to dampen the TRH effects on various behavioral responses.     

Influence of mouse strain, infective dose and larval burden in the brain on activity in Toxocara-infected mice

Outbred LACA mice and inbred NIH mice were administered low (100 ova), medium (1000 ova), high (3000 ova) and trickle (4x250 ova) doses of Toxocara canis ova and the effect of infection on activity was examined with respect to: (i) the dose of ova administered and (ii) the number of larvae recovered from the brain. Larval recovery from the brain was significantly reduced in NIH mice compared to LACA mice for the 1000, 3000 and trickle doses. Mice from each strain were divided into larval intensity groupings based upon the number of larvae recovered from their brain. Activity for each mouse was measured pre- and post-infection by observing its behaviour in the home cage. Activity was assessed by monitoring six different independent categories of murine behaviour - ambulation, grooming, rearing, digging, climbing and immobility. Within each behavioural category, the duration of time spent at each behaviour per mouse within one thousandth of a second, the number of short bouts performed and the number of long bouts of behaviour performed were recorded over a 20 min period. Activity of LACA and NIH mice differed prior to infection. LACA mice spent more time immobile compared to NIH mice, which ambulated and climbed more. Variations in activity were also observed between groups of mice prior to infection. The effect of infection differed by strain, by dose and by larval intensity. Post-infection LACA mice became more immobile and ambulated less. NIH mice showed reduced immobility, but while ambulation decreased digging and climbing increased post-infection. Short bouts of activity remained unchanged among LACA mice post-infection but showed an increase for some behaviours in NIH mice.     

Ligands of the NMDA receptor-associated glycine recognition site and motor behavior

Summary Motor behavior critically depends on glutamatergic functions in the basal ganglia (BG). The dorsal and ventral striatum — the main input structures of the BG - are involved in modulation of stereotyped sniffing behavior, locomotion, catalepsy and prepulse inhibition. The effects of the NMDA receptor have been well characterized in respect to motor behavior in the past. The function of the allosteric glycine site was however disregarded until now, because brain penetrating ligands were missing. The present study summarized the motor behavioral profile of several glycine site ligands (7chlorokynurenate, ACEA 1021, MRZ-2/576, (+) HA-966, D-cycloserine and felbamate). It is shown that through blockade of the glycine site of the NMDA receptor a distinct behavioral profile can be obtained.     

Rats rapidly develop tolerance to the locomotor-inhibiting effects of the novel neuropeptide orphanin FQ

We examined the effects of intracerebroventricular (i.c.v.) administration of orphanin FQ (OFQ) on locomotor activity in rats. The rats were habituated to locomotor-testing boxes and then injected i.c.v. with OFQ (0–10 nmoles). Acute injections of OFQ produced dose-orderly reductions in horizontal locomotion and rearing activity. This suppression of motor activity was characterized by a disruption of balance and muscle control. Within minutes of i.c.v. injection of the higher doses of OFQ, the rats exhibited flaccid muscle tone. They each lay in an atypical posture, pressing the abdomen against the floor, and splaying the hindlimbs. When these rats locomoted, their gate was unsteady. They wobbled from side to side, and frequently fell over. Repeated daily injections of OFQ resulted in a rapid development of tolerance to the OFQ-induced suppression of locomotion and rearing activity. Tolerance to the observed impairments of motor control were also apparent. In the rats that were repeatedly treated with the highest dose (10 nmol) of OFQ, tolerance to the motoric effects was still apparent after 7 days without OFQ treatment. Special issue dedicated to Dr. Eric J. Simon.     

Functional alteration by NMDA antagonist: effects of L-Dopa,neuroleptics drug and postnatal administration

Summary.  Antiakinsic effects of the uncompetitive NMDA antagonists, memantine, amantadine and MK-801, and competitive antagonists, CGP 40116, alone or in co-administration with acute subthreshold dose of L-Dopa (5 mg/kg) in MPTP-treated mice, functional alterations induced by acute MK-801 in combinations with neuroleptic compounds or behavioural deficits following postnatal administration of MK-801 were investigated. Memantine and amantadine injected 60 min before the subthreshold dose of L-Dopa (5 mg/kg), induced antiakinesic actions in hypokinesic MPTP-treated mice. Concurrently, higher doses of memantine and MK-801 caused dyskinesic changes, reducing further rearing (10 and 30 mg/kg) and locomotor (30 mg/kg) behaviour of the MPTP mice; MK-801 elevated locomotion (0.1 mg/kg) but reduced rearing (0.3 mg/kg). In control, saline-treated mice, memantine (3, 10 and 30 mg/kg) and MK-801 (0.1 and 0.3 mg/kg) increased locomotor behaviour but decreased rearing behaviour. In rats, MK-801 induced marked increases in locomotor activity and disruptions of circular swim maze acquisition that were to greater or lesser extents blocked or potentiated by neuroleptic compounds: SCH 23390 (0.005 and 0.05 mg/kg) and clozapine (5.0 and 10.0 mg/kg) dose-dependently antagonised MK-801 (0.3 mg/kg) induced locomotor activity whereas raclopride (0.1 mg/kg) and haloperidol (0.1 mg/kg) attenuated it dose-specifically. Amperozide (0.5 mg/kg) attenuated the MK-801 effect but potentiated it at the 2.0 mg/kg dose. In the circular swim maze, raclopride (0.01 mg/kg) and SCH 23390 (0.05 mg/kg) improved the acquisitive performance of rats administered MK-801 (0.03 mg/kg) acutely whereas clozapine (10.0 mg/kg) and amperozide (2.0 mg/kg) deteriorated the performance of MK-801-treated rats. Postnatal administration of MK-801 (0.05 mg/kg, day 11 after birth) induced severe functional alterations in adult mice. At 70 days of age, MK-801 mice showed an initial hypoactivity followed by marked hyperactivity in the motor activity test chambers. These mice showed deficits in habituation, a nonassociative form of learning. Their hyperactivity in the test chambers was reversed by a low dose of d-amphetamine (0.25 mg/kg). Taken together, these findings display a wide range of acute/long-term functional alterations induced by NMDA antagonists, particularly MK-801, associated with animal models of brain disorders. Received July 9, 2001 Accepted August 6, 2001 Published online June 17, 2002     

Glutamate receptors and the airways hyperreactivity

It is proposed the link between the hyperactivity of NMDA receptors and airway hyperresponsiveness. We investigated the effect of agents modulating the activity of NMDA receptors in the ovalbumin-induced airway hyperreactivity in guinea pigs. The airways hyperreactivity was influenced by the agonist (NMDA) and selective antagonist - competitive (AP-5) and non-competitive (MK-801) of NMDA receptors. Airway responsiveness to histamine or acetylcholine was evaluated in in vitro conditions. NMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. MK 801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle, while the former, non-competitive antagonist was more effective. We recorded more pronounced response in tracheal than in lung tissue smooth muscle with more considerable response to acetylcholine than to histamine. The results of experiments show the modification of airway smooth muscles responses by agents modulating the activity of NMDA receptors. They confirm the possibility of NMDA receptors participation in experimental airway hyperreactivity. The results enlarge information regarding the link of the inflammatory diseases and glutamatergic system.     

Infusions of acetaldehyde into the arcuate nucleus of the hypothalamus induce motor activity in rats

AimsThe hypothalamic arcuate nucleus (ARH) is one of the brain regions with the highest levels of catalase expression. Acetaldehyde, metabolized from ethanol in the CNS through the actions of catalase, has a role in the behavioral effects observed after ethanol administration. In previous studies acetaldehyde injected in the lateral ventricles or in the substantia nigra reticulata (SNR) mimicked the behavioral stimulant effects of centrally administered ethanol.Main methodsIn the present study we assessed the effects of acetaldehyde administered either into the ARH into a dorsal control or into the third ventricle on locomotion and rearing observed in 30 min sessions in an open field.Key findingsAcetaldehyde injected into the ARH induced horizontal locomotion and rearing for 20 min. In contrast, administration of acetaldehyde into a control site dorsal to the ARH did not have any effect on locomotion. Although acetaldehyde administration into the third ventricle also induced locomotion, the time course for the effect in this area was different from the time course following ARH injections. Acetaldehyde in the ARH produced a long lasting induction of locomotion, while with intraventricular injections the effects disappeared after 5 min.SignificanceThe present results are consistent with previous studies demonstrating that acetaldehyde is an active metabolite of ethanol, which can have locomotor stimulant properties when administered in the ventricular system of the brain or into specific brain nuclei. Some brain nuclei rich in catalase (i.e.; SNR and ARH) could be mediating some of the locomotor stimulant effects of ethanol through its conversion to acetaldehyde.     

Interaction between N-methyl-D-aspartate receptor antagonists and imipramine in shock-induced depression

In the past few years, literature has accumulated describing manifestation of seizures following administration of certain antidepressants. Such reports are of particular importance because depression is a frequent psychiatric problem associated with epilepsy. Therefore, in the view of the fact that NMDA receptor antagonists have been reported to reduce behavioural deficits and have been shown to be anticonvulsant, it was considered imperative to study their antidepressant effect using shock-induced depression model in mice. Presentation of inescapable foot shock significantly reduced ambulation and rearing in the open field arena and increased immobility duration in the FST. Pretreatment with imipramine, MK 801 and ketamine significantly prevented the effect of shock. Also, the combination of imipramine with either of the NMDA antagonists antagonised the effect of shock. Haloperidol, prazosin and ketanserin pretreatment modified the effect of these agents. These findings suggest an antidepressant effect of the NMDA receptor antagonists, and a complexity of neurotransmitter mechanisms, which are responsible for the occurrence of behavioural effects in shock-induced depression model.