Biomedical subjects

B M Spruijt

Publications and source records attributed to B M Spruijt.

At least 19 recordsLinked to original sources

PubMed1997

Postoperative environmental enrichment attenuates fimbria-fornix lesion-induced impairments in Morris maze performance.

Male Wistar rats were given a bilateral or a unilateral transection of the fimbria-fornix; subsequently they were kept in standard laboratory housing conditions or in enriched environments for 6 weeks, after which they were tested in the Morris maze. In the acquisition phase of the experiment rats with a bilateral lesion of the fimbria-fornix were markedly impaired in their ability to locate the hidden platform, while rats with unilateral lesions displayed no such impairment. However, rats with a bilateral lesion displayed a less severe deficit when they had been housed postoperatively in the enriched environment. In the retention phase of the experiment rats with a bilateral lesion swam markedly less time in the platform zone only when they had been housed in standard conditions. They also spent more time in the edge zone than the other groups. Rats with a bilateral lesion that were housed enriched did not swim more in the edge zone. Despite their good performance during acquisition they did not display a clear preference for the platform zone. Thus, it was speculated that enriched rats with a bilateral lesion had learned to leave the side of the pool to search for the platform and with the aid of this different strategy improved their performance.

Animals↗

PubMed1996

Chronic and intra-amygdala administrations of the ACTH(4-9) analog ORG 2766 modulate behavioral changes after manipulation of NMDA-receptor activity.

Microinjection of N-methyl-D-aspartic acid (NMDA, 300 ng/3 microliters) into the left lateral ventricle causes a substantial increase in locomotor activity which can be significantly reduced by a chronic pretreatment with the ACTH(4-9) analogue ORG 2766(1 microgram/0.5 ml saline, subcutaneous (s.c.) every day for 7 days, last injection 24 h before the NMDA-injection). A single dose of ORG 2766 (1 ng/1 microliter) injected into the left central amygdaloid nucleus 30 min before the NMDA-injection was equally effective in reducing the increase in locomotion. Furthermore it counteracted the predominance of contralateral turning induced by the NMDA-injection. The data give support for the idea that ORG 2766 excerts its effects on behavior and neural recovery by modulating NMDA receptor activity in the brain.

Adrenocorticotropic Hormone↗

PubMed1996

Roles of the basolateral amygdala and hippocampus in social recognition in rats.

Lesions of the amygdala or hippocampus have a large impact on social behavior of rats. In this study we investigated whether a social recognition test was also affected by those lesions. An NMDA-induced lesion of the basolateral amygdala did not impair the ability to distinguish a familiar from an unfamiliar juvenile rat. It was argued that the cortico-medial amygdala may be more important for social recognition than the basolateral amygdala. Fimbria-transected rats could no longer distinguish a familiar from an unfamiliar juvenile. Moreover, during all encounters they spent less time investigating the juvenile. The precise nature of this deficit, especially the reason for the overall reduced social investigation time, could not be specified with the classical procedure of the social recognition test.

Amygdala↗

PubMed1996

ACTH(4-9) analog ORG2766 treatment 7 months delayed still improves morris maze performance of fimbria-lesioned rats.

The ACTH(4-9) analog ORG2766 has been known to affect recovery of damaged functions resulting from injury to neural tissue. The peptides efficacy has often been ascribed to a facilitation of existing recovery, and immediate treatment seemed a prerequisite for efficacy. However, various results in other recovery paradigms do not refer to the neurotrophic properties of the peptide, but rather ascribe the effectiveness of ORG2766 to a general change in attention that indirectly affects functional recovery. Such a change in state is theoretically independent of the occurrence of spontaneous recovery, and, thus, treatment would not be required to coincide with recovery immediately after the damage. To see if ORG2766 can influence the recovery of function without the simultaneous occurrence of spontaneous recovery, this study employed a delay of 7 months after the occurrence of a fimbria lesion before ORG2766 was administered. The selective fimbria lesion produced an impairment in Morris maze performance, which could be attenuated by chronic treatment with ORG2766 immediately after the lesion as well as after 7 months. With respect to spatial orientation, no improvement is assessed in untreated lesioned rats, as the impairment of Morris maze performance in untreated fimbria-lesioned rats is as severe as right after the lesion. The data indicates that efficacy of the ACTH(4-9) analog does not rely on the acceleration of spontaneous recovery processes in this paradigm. The behavioral effects of ORG2766 are discussed in the context of a peptide-induced state of enhanced attention.

Adrenocorticotropic Hormone↗

PubMed1996

The ACTH(4-9) analog ORG 2766 and recovery after brain damage in animal models--a review.

Treatment with adrenocorticotrophic hormone (ACTH), as well as with ACTH fragments and analogues, can influence behaviour of animals and humans. Furthermore it facilitates recovery of damaged peripheral nervous tissue. The question whether ACTH/MSH peptides affect recovery processes after injury to the central nervous system as well is addressed in the present review. The effects of administration of the ACTH(4-9) analog ORG 2766 after brain lesions has been studied frequently. However, the interpretation of the available data is confused by the variability of the results. Several factors can be identified which influence the efficacy of the peptide: (i) not all behavioural tests are equally suitable to reveal a peptide effect on behavioural recovery; (ii) the affected brain area; (iii) whether cell bodies or terminals are affected; (iv) the post-operative housing conditions; and (v) the onset and duration of peptide administration. Two possible explanations of peptide efficacy on functional recovery are considered: first, the peptide may accelerate spontaneously occurring recovery processes and second, the peptide may induce compensatory mechanisms underlying functional recovery without recuperation of the damaged neurons. These compensatory mechanisms seem to rely mainly on enhanced non-selective attention by activation of limbic structures. It is as yet unknown to which receptor system ORG 2766 binds; the analog lacks affinity for the known melanocortin (MC) receptors in brain, yet ORG 2766 is able to modulate the activity of endogenous opioids and the NMDA-receptor. A modulating influence of the peptide on NMDA-receptor activity might indirectly account for both enhanced attention--with ensuing behavioural recovery--and the acceleration of spontaneous recovery.

Adrenocorticotropic Hormone↗

PubMed1996

Long-term impoverished housing effects on Morris maze performance after a fimbria lesion.

Male Wistar rats received bilateral Fimbria lesions and were postoperatively housed in either standard social conditions or in impoverished conditions (one rat per cage) for 2 weeks in experiment I, and for 7 months in experiment II. The effects of lesion and housing conditions were investigated in the Morris maze spatial orientation task. Fimbria lesions increased the latency to reach the platform during acquisition in both experiments, which indicates that functional recovery of the Morris maze impairment does not occur in 7 months time. Post-operative impoverishment for 2 weeks or for 7 months reduced the lesion induced deficit in Morris maze acquisition, while it had a more general effect in the trial without platform. Interestingly, the impoverishment effects were not more severe after 7 months, but even less easily detected. These findings are interpreted as if impoverishment effects the reactiveness of animals to external stimuli, which may help the animal to compensate for the lesion-induced-deficit in Morris maze learning.

Animals↗

PubMed1996

Effects of an electrolytic lesion of the prelimbic area on anxiety-related and cognitive tasks in the rat.

The aim of this paper was to study the role of the prelimbic area of rats in response selection. A bilateral electrolytic lesion was made in the prelimbic area. The rats were tested in the Morris water-maze, the conditioned shock-prod burying test, the elevated plus-maze, a modified open field test, and the step-through passive avoidance test. In the water-maze during initial acquisition, the latency times of the lesioned rats were not different from those of the controls, but they found the platform faster than the sham operated rats after the platform was placed in a new position. The lesion did not affect performance in the shock-prod burying test. In the elevated plus-maze the lesioned rats were more active than the sham-operated rats and spent more time on the open arms. In the open field there was no difference between lesioned and sham-operated rats with regard to distance travelled or the time spent near the object in the center of the open field. In the passive avoidance test the lesioned rats had a shorter latency time to enter the shock compartment during the retention trial than the sham-operated rats did. The results were discussed in relation to those of similar studies. The extent and precise localisation of the lesion seems to be crucial for the outcome: lesions confined to the prelimbic area may have the opposite effects of larger lesions. Furthermore, it may well be that the prelimbic area is only involved in processing of stimuli of a specific sensory modality, as made probable by the results of different conditioned reinforcement tasks. Finally, it was stated that we still lack a hypothesis about the precise role of the prelimbic area in response selections.

Animals↗

PubMed1996

Mechanical lesions of the fimbria fornix in rat brain studied by 1H-magnetic resonance imaging. Evidence for long-lasting dynamic alterations in the ipsilateral ventricular system.

In vivo 1H-NMR imaging was employed to study dynamic changes in the status of tissue water as a function of time after mechanical brain injury induced by partial unilateral transection of the fimbria fornix (FF) in the rat brain and was correlated with histology. Changes in the brain tissue were reproducibly found in distinct regions which were exclusively located in the lesioned hemisphere. The most pronounced changes concerned the lateral ventricle. Ventricular enlargement became evident posterior to the site of transection after a few hours and was maximal after 2-4 days. At later time points the posterior ventricular expansion was reduced. The lateral ventricle anterior to the site of transection was significantly enlarged from day 1 and continued to expand for up to 7 months. Tissue response at the site of transection, mainly involving the hippocampal formation and the thalamus, was first manifested after 24 h, while signs of progressive tissue degeneration were apparent in the long term.

Animals↗

PubMed1996

Prenatal exposure to morphine affects juvenile play behavior and adult social behavior in rats.

The effects of morphine exposure in utero on play behavior and social behavior were investigated in a longitudinal study. Wistar rat dams were SC injected daily with saline (control) or 10 mg/kg morphine from day 8 to day 21 of gestation. Play behavior of the offspring was measured at 3 and 4 weeks of age and social behavior at 3 months of age. Pinning, a measure for play behavior and social grooming of the morphine-treated offspring were significantly elevated compared to saline controls, especially on day 21. The onset-latency of pinning behavior was not changed. Furthermore, prenatal morphine treatment resulted in more social approach and less social avoidance behavior in adulthood, whereas changes in general locomotor activity were not observed. The results are discussed in relation to the effects of in utero exposure of morphine on the development of incentive aspects of play and social behavior.

Animals↗

PubMed1996

Chronic administration of Org2766 and morphine counteracts isolation-induced increase in social interest: implication of endogenous opioid systems.

In complex behaviors, like social behavior, the MSH/ACTH (4-9) analog Org2766 is found to counteract changes in social interest caused by preceding housing or test conditions. Previous studies have indicated an involvement of endogenous opioid systems in these outcomes. In the present study we have counteracted isolation-induced enhanced social interest by chronic treatment (7 x every 48 h) with Org2766 or with the opiate morphine. These effects were blocked by previous administration of naloxone. However, in group-housed animals, both Org2766 and morphine treatment did not result in changes in social activity as compared to saline-treated group-housed controls. Chronic administration of naloxone in group-housed rats resulted in an increase in social interest. These results are discussed in relation to possible function of Org2766 and morphine as a substitute for the release of endogenous opioids caused by social contact.

Adrenocorticotropic Hormone↗

PubMed1996

Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats.

Moderate impairment of learning and memory has been recognized as a complication of diabetes. The present study examined behavioral and electrophysiological measures of cerebral function in streptozotocin (STZ)-induced diabetic rats. Behavioral testing consisted of a spatial learning task in a water maze. Electrophysiological testing consisted of in vitro assessment of hippocampal long-term potentiation (LTP), an activity-dependent form of synaptic plasticity, which is believed to be related to the cellular mechanisms of learning and memory. Two experiments were performed: the first with severely hyperglycemic rats and the second with moderately hyperglycemic rats. Rats were tested in the water maze 11 weeks after induction of diabetes. Next, LTP was measured in vitro in trained animals. Both spatial learning and LTP expression in the CA1 field of the hippocampus were impaired in severely hyperglycemic rats as compared with nondiabetic controls. In contrast, spatial learning and hippocampal LTP were unaffected in moderately hyperglycemic rats. The association of alterations in hippocampal LTP with specific learning impairments has previously been reported in conditions other than diabetes. Our findings suggest that changes in LTP-like forms of synaptic plasticity in the hippocampus, and possibly in other cerebral structures, are involved in learning deficits in STZ-induced diabetes. The beneficial effect of moderate glycemic control on both place learning and hippocampal LTP supports the significance of the relation between these two parameters and indicates that the development of the observed deficits may be related to the level of glycemic control.

Animals↗

PubMed1995

Sequential analysis of social play behavior in juvenile rats: effects of morphine.

The effects of morphine on social play behavior in juvenile rats were investigated using sequential analysis. Social play behavior of 21-day-old rats treated with 1.0 mg/kg of morphine or saline was analyzed for 15 min. Frequencies and durations of measures of social play behavior, such as pinning, boxing/wrestling and following/chasing were significantly increased after treatment with morphine. Social behaviors not related to play, such as social exploration and crawling over/under were slightly decreased, while social grooming and non-social behavior were not affected by morphine treatment. Using sequential analysis, the dissociation between social behaviors related and unrelated to play was confirmed. Pinning and boxing/wrestling were highly significantly associated. In addition, crawling over/under significantly often preceded social grooming, and an association between social exploration and non-social behavior was found as well. Pinning and boxing/wrestling appeared to be negatively associated with non-social behaviors, social exploration and crawling over/under. A negative association between social grooming and social exploration was also found. Upon treatment with morphine, no major effects on the sequential structure of social behavior were observed: pinning and boxing/wrestling appeared more associated with following/chasing, and the negative association between pinning and boxing/wrestling on the one hand and social exploration on the other was enhanced. Thus, morphine slightly increased the coherence of social play behavior. It is concluded that morphine exerts its effects on social play behavior by increasing social play behavior as a whole rather than by changing its structure, suggesting a key role for opioid systems in the regulation of social play behavior.

Aggression↗

PubMed1995

Mu- and kappa-opioid receptor-mediated opioid effects on social play in juvenile rats.

Previously, morphine has been shown to influence social play behavior in rats on two levels. An increasing effect on social play was interpreted as an effect on the rewarding aspects of social play. A lower dose of morphine abolished the effects of an unfamiliar environment on social play, supposedly by affecting the integration of environmental stimuli. In the present study the effects of receptor-specific opioid drugs on social play and measures of social behavior unrelated to play were investigated. Fentanyl, a mu-opioid receptor agonist, seemingly mimicked both effects of morphine. The mu-opioid receptor antagonist, beta-funaltrexamine, decreased social play, although a low dose of this drug increased it. BUBUC (Tyr-D-Cys(StBu)-Gly-Phe-Leu-Thr(OtBu)) and naltrindole, a delta-opioid receptor agonist and delta-opioid receptor antagonist, respectively, had no effects on social behavior. The kappa-opioid receptor agonist, U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide), dose dependently suppressed all measures of social behavior. The kappa-opioid receptor antagonist, nor-binaltorphimine, abolished the effect of an unfamiliar environment on social play. These studies suggest that the opioidergic effect on social play is mediated through mu- and kappa-opioid receptor systems.

Amino Acid Sequence↗

PubMed1995

Effects of morphine on different aspects of social play in juvenile rats.

To clarify the influence of opioids on social play, the effects of morphine on playful and non-playful social behavior in juvenile rats was investigated under different conditions. Environmental variables employed were different (dim and intense) levels of illumination during testing, familiarity to the test cage, and different periods of social isolation prior to testing. Under dim light conditions, morphine markedly increased playful social behavior, such as pinning, boxing/wrestling and following/chasing, whereas non-playful social behavior such as social exploration and contact behavior was hardly affected. This effect of morphine was independent of duration of previous isolation and dose-dependent, with a maximal effect at 1.0 mg/kg. The mechanism of this effect is interpreted as an action on the rewarding aspects of play. A dose of 0.1 mg/kg of morphine abolished the initial suppression of play induced by unfamiliarity to the test cage, without influencing total levels of play. This may be an effect of morphine on the integration of sensory stimuli. Under intense light conditions, whereas playful behavior was completely suppressed, morphine itself hardly affected such behavior, but decreased some aspects of non-playful social behavior. These results suggest that in juvenile rats playful and non-playful forms of social behavior are differentially regulated. In addition, opioid systems may be involved at different levels in the regulation of social play.

Animals↗

PubMed1995

Influence of environmental factors on social play behavior of juvenile rats.

The effects of light level and familiarity to the testing environment on social behaviors related and unrelated to play were investigated in juvenile rats accustomed to dim light conditions. Pinning, a measure characteristic for social play in rats, was completely suppressed under intense light conditions. Following/chasing and boxing/wrestling, social behaviors related to play, were also decreased under intense light. Of the measures of social behavior not related to play, contact behavior was decreased under intense light whereas social exploration was hardly affected. Levels of social exploration and following/chasing gradually declined during the 15-min test period. Frequency of contact behavior decreased, whereas duration increased with time. Under dim light conditions, unfamiliarity to the test cage suppressed pinning and boxing/wrestling but not the other social behaviors in the first part of the test period. These findings show that social behavior in juvenile rats, as in adult rats, can be influenced by light level and familiarity to the test cage. Social behaviors related and unrelated to play seem to be differentially influenced by environmental stimuli.

Animals↗

PubMed1995

Olfactory bulbectomy temporarily impairs Morris maze performance: an ACTH(4-9) analog accellerates return of function.

Rats with a bilateral lesion of the olfactory bulb are permanently anosmic. However, this lesion also produces nonspecific behavioral effects that recover over time. In this study olfactory bulb-lesioned animals are given a spatial orientation task--the Morris maze--which supposedly relies on visual and not olfactory cues. In exp. 1 this assumption was verified by subjecting animals with peripherally induced anosmia to the Morris maze (olfactory neurons in the nasal mucosae were destroyed by flushing the nose with ZnSO4). Anosmia did not affect the acquisition rate of the animals. In exp. 2 anosmia was produced by a central lesion to the bulbus olfactorius. Two weeks after lesioning the Morris maze performance is severely impaired. Interestingly, chronic administration (10 micrograms/48 h/rat, during these 14 days, SC) of the ACTH(4-9) analog ORG 2766 diminished the impairment in performance. In exp. 3 olfactory bulb-lesioned animals were allowed 6 wk to recover before Morris maze testing began, to investigate if spontaneous recovery of performance occurred. No difference was seen in the acquisition performance of lesioned animals when compared to sham animals at this timepoint. The effect of the peptide is discussed in the context of an acceleration of the recovery of nonspecific consequences of brain lesioning.

Adrenocorticotropic Hormone↗

PubMed1994

The effect of haloperidol and naloxone on excessive grooming behavior of cats.

In a double-blind cross-over study the effect of a single injection of naloxone (1 mg/kg s.c.) was investigated in 12 cats which suffered from excessive grooming with subsequent coat damage. Based on clinical observations and reports of the owners, naloxone had a beneficial effect on grooming which lasted between 2.5 weeks and 6 months (median 3 months). In another double-blind placebo-controlled study the effect of a single injection of haloperidol (2 mg/kg i.v.) was investigated in 20 cats with excessive grooming. Within 24 h haloperidol significantly reduced the time spent grooming. Four months after the injection no effect remained in nine of 10 cats injected with a placebo solution, whereas six of 10 cats injected with haloperidol the improved condition of the coat was maintained. It is hypothesized that naloxone is only effective in counteracting recently developed stereotypic behaviors and that haloperidol rather reduces stereotyped behaviors over a longer period.

Alopecia↗

PubMed1994

Spatial localization in the Morris water maze in rats: acquisition is affected by intra-accumbens injections of the dopaminergic antagonist haloperidol.

Previous studies (G. E. Ploeger, B. M. Spruijt, & A. R. Cools, 1992) showed that low doses of systemically injected haloperidol affected spatial learning in the Morris water maze. This study investigated effects of intra-accumbens injections of haloperidol on spatial learning. To control for motivation and sensorimotor coordination, the researchers trained the rats to escape onto a visible platform. Low doses (50-100 ng) of haloperidol impaired spatial learning, whereas escaping on a visible platform was undisturbed. The 500-ng dose of haloperidol completely blocked acquisition because of combined learning and motor impairments. Retrieval of an acquired escape response was unaffected by 500 ng haloperidol. The data show that mesolimbic dopaminergic activity is involved in the acquisition of spatial localization. The results are related to studies demonstrating the involvement of the nucleus accumbens in cue-directed behaviors.

Animals↗