Biomedical subjects

J M van Ree

Publications and source records attributed to J M van Ree.

At least 19 recordsLinked to original sources

PubMed1992

The use of adrenocorticotrophic hormone (4-9) analog ORG 2766 in autistic children: effects on the organization of behavior.

In a double-blind placebo-controlled crossover trial, 14 autistic children were treated with the neuropeptide ORG 2766, a synthetic analog of adrenocorticotrophic hormone (ACTH) (4-9). ORG 2766 treatment (20 mg per day during 4 weeks) was associated with an increased amount and an improved quality of the social interaction of the autistic children with a familiar experimenter. These changes in interaction were clinically relevant. Following treatment with ORG 2766 gaze and smile behaviors of child and experimenter showed stronger temporal contingencies. Further, after ORG 2766, stereotypies were temporally disconnected from verbal initiatives. The data supported the notion of a stimulating effect of ORG 2766 on social interaction. The implications of these findings for the endogenous opioid theory of autism are discussed.

Adrenocorticotropic Hormone↗

PubMed1992

Deficits in social behavior in autism and their modification by a synthetic adrenocorticotrophic hormone (4-9) analog.

When charting the structure of the social behavior of autistic children by means of an ethologically analyzed playroom session, deficits appeared in the reciprocity of eye-contact and in the location of verbal initiatives. These deficits in social behavior were beneficially influenced by treatment with the adrenocorticotrophic hormone (4-9) analog ORG 2766.

Adrenocorticotropic Hormone↗

PubMed1992

Low doses of oxytocin facilitate social recognition in rats.

Social recognition of juveniles by adult male residents has been shown to be modulated by neurohypophyseal hormones. The decrease of social investigation behavior during a second encounter with the same juvenile serves as index for social recognition. In the present study it was found that low doses (0.09-6.0 ng.kg-1) of oxytocin (OXT) given subcutaneously dose dependently facilitated social recognition. The effect of OXT appeared specific, since no change in social investigation was found when a novel juvenile was tested during the second encounter. No disturbances of social recognition by the low doses of OXT could be detected, in contrast to higher doses of this hormone. Other neurohypophyseal hormones, vasopressin and vasotocin, did not facilitate social recognition when tested in the same range of low doses.

Animals↗

PubMed1992

Stimulation of the pituitary-adrenal axis with a low dose [Arg8]-vasopressin in depressed patients and healthy subjects.

Graded doses arginine-vasopressin (AVP) were administered to depressed patients and control subjects to compare the sensitivity of the pituitary-adrenal system of these subjects for this compound. The plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin were measured before and after intravenous AVP injection. The hormonal output was taken as a measure of pituitary-adrenal function. In control subjects 3 doses AVP and placebo were used, whereas in patients two doses AVP, a low and a high dose, and placebo were tested. All tests were carried out in the afternoon when the pituitary-adrenal system is stable and more susceptible for stimulation. Patients were subdivided into dexamethasone suppressors and nonsuppressors based on their DST status before testing to look for differences among these groups. Control subjects showed no response of the hormones to the lowest dose AVP and a moderate response to the higher doses. Interestingly, depressed patients as compared to controls responded more to the lowest dose AVP in particular with respect to ACTH. DST status did not influence the results. These findings suggest an enhanced sensitivity of the pituitary to low doses AVP in depressed patients. Thus, AVP might play a role in HPA dysfunction in depression.

Adrenocorticotropic Hormone↗

PubMed1992

Low doses of morphine reduce voluntary alcohol consumption in rhesus monkeys.

Experimental opioid modulation has been found to influence the consumption of alcohol in animals. Whereas it has generally been agreed upon that opiate antagonists reduce alcohol consumption, the results with opiate agonists are less consistent. The present study reports on the effect of low doses of morphine in 8 adult male rhesus monkeys that had a free choice in drinking water, a 16% and a 32% ethanol/water solution, (a) during continuous ad libitum access (Experiment I), and (b) after 2 days of alcohol abstinence (Experiment II). In both experiments each monkey received a single morphine injection (i.m.) in 5 different doses (0.03, 0.06, 0.17, 0.50, 1.50 mg.kg-1); each morphine injection (i.m.) was placebo-controlled in a cross-over design. Consumption was measured from 16.00 h in the afternoon (30 min after injection) to 08.30 h the next morning. In Experiment I after 0.50 and 1.50 mg.kg-1 of morphine ethanol intake and water consumption were both reduced during the first hours after injection; only ethanol intake remained reduced during the subsequent night. Effects lasted not longer than 24 h. In Experiment II, morphine administered 30 min before reintroduction of ethanol solutions reduced ethanol intake at doses of 0.17, 0.50 and 1.50 mg.kg-1; water consumption was unaffected. The reduction lasted for the subsequent night after the 2 highest doses. Records obtained of various spontaneous behavioural activities made it unlikely that the used dose range had induced some aspecific sedation; monkeys remained alert and active. The results are contradictory with studies in which low doses of morphine stimulated alcohol drinking in rats. The present results seem to support the hypothesis that at least in monkeys morphine can compensate for some effects of alcohol.

Alcohol Drinking↗

PubMed1991

Structural modifications of the ACTH-(4-9) analog ORG 2766 yields peptides with high biological activity.

The behavioral effects of two peptides (HOE 427) and ORG 31433) related to the ACTH-(4-9) analog ORG 2766 were investigated in Wistar rats in a number of tests in which Org 2766 is active. Subcutaneous administration of HOE 427 in a dose of 0.5 ng/kg or ORG 31433 in doses of 0.5-5.0 ng/kg facilitated passive avoidance behavior whereas these peptides attenuated the avoidance response in doses of 25 ng/kg and 250 ng/kg respectively. ORG 31433 (0.1 - 1.0 microgram/kg) decreased motor activity of group housed rats tested under low light conditions. Furthermore subcutaneous (1.0- 10.0 ng/kg) or oral (10 microgram/kg) administration of ORG 31433 accelerated functional recovery from 6-hydroxydopamine (6-OHDA)-induced lesions in the nucleus accumbens which cause motor hypoactivity. The experiments show that as compared to ORG 2766 the peptides HOE 427 and ORG 31433 induce qualitatively similar responses but are approximately 10 to 100 times more potent. These data may imply that substitution of the C-terminal COOH group of ORG 2766 yields neuropeptides with increased potency.

Administration, Oral↗

PubMed1991

Neuropeptides related to [Arg8]vasopressin facilitates social recognition in rats.

The decrease of social investigations of adult rats during a second encounter session with the same juvenile was used as an index of social recognition or memory. Social recognition was present when the interexposure interval was 15 or 30 min, but not when this interval lasted 60 or 120 min. Animals treated with desglycinamide[Arg8]vasopressin (DGAVP) (6.0 micrograms.kg-1, SC) or [pGlu4,Cyt6]AVP-(4-8) (AVP-(4-8] (1.0 microgram.kg-1, SC), immediately after the first encounter, recognized the same juveniles still after 120 min, suggesting a facilitatory effect of these peptides on social recognition and that this effect of vasopressin is dissociated from the classical endocrine effects of this hormone. The decrease of social investigating behavior, in both placebo- and DGAVP-treated rats, was completely due to a decrease in anogenital exploration, indicating that the social recognition in rats is presumably based on odor cues from the anogenital part of the body.

Animals↗

PubMed1991

Short duration of retroactive facilitation of social recognition in rats.

Adult rats spent less time investigating the same juvenile during a second dyadic encounter session. This decrease served as an index for social recognition. Social recognition was not influenced by isolating the juveniles for 7 days prior to experimentation. Retroactive facilitation of social recognition was observed when the two rats were confronted for a longer period of time on a given day by multiple testing. However, this facilitation was not observed after a 24-h interexposure interval between encounter sessions, even when different housing conditions during that time were taken into account, and animals were tested during 5 consecutive days. It is suggested that social recognition may be a form of short-term memory.

Aging↗

PubMed1991

Intracerebroventricular naltrexone treatment attenuates acquisition of intravenous cocaine self-administration in rats.

The influence of centrally administered naltrexone, an opiate antagonist, on acquisition of intravenous cocaine self-administration behaviour in rats was examined. On five consecutive days, three hours per day, they could self-administer a cocaine solution (30 micrograms per infusion) through an indwelling cannula. Treatment consisted of daily injections of naltrexone (2 or 5 micrograms) or placebo into the lateral ventricle 30 minutes before testing. Naltrexone treatment dose dependently attenuated the rate of cocaine self-infusion. Both self-infusion rate and rate of responding on the reinforcement lever in the group treated with 5 micrograms naltrexone differed from placebo, whereas rate of responding on a dummy lever did not. These findings a) support the notion that opioid systems play a role in cocaine reinforcement, and b) suggest that naltrexone exerts its effect on cocaine reinforcement through action in the central nervous system.

Animals↗

PubMed1991

Oxytocin but not vasopressin facilitates social recognition following injection into the medial preoptic area of the rat brain.

Social recognition of juvenile rats by adult male residents has been shown to be modulated by peripheral administration of neurohypophyseal hormones vasopressin and oxytocin. In the present study, the effects of these peptides on social recognition were investigated after local injection into the medial preoptic area of the hypothalamus. It was found that oxytocin given in a wide range of doses (0.3-1000 pg) facilitated social recognition. This effect was not blocked by pretreatment with oxytocin receptor antagonist desGly(NH2)9-d(CH2)5[Tyr(Me)2Thr4]OVT. Oxytocin injected into the septum in doses of 0.03-3 pg was not effective. Administration of vasopressin (100 or 1000 pg), [pGlu4,Cyt6]AVP-(4-8) (200 pg) or [pGlu4,Cyt6]AVP-(4-9) (200 pg) into the medial preoptic area did not influence social recognition. It is concluded that the medial preoptic area is a sensitive brain site for the oxytocin-induced facilitation of social recognition in rats.

Angiotensin Receptor Antagonists↗

PubMed1991

Analysis of the influence of vasopressin neuropeptides on social recognition of rats.

The facilitatory effect of vasopressin neuropeptides on social recognition of adult male rats was analyzed. The decrease of social investigation behaviors during a second encounter with the same juvenile rat served as index for social recognition. Treatment with desglycinamide-(Arg8)-vasopressin (6 mg.kg-1, s.c.) extended the time that adults recognize the same juvenile from 30 min to 24 h. Structure-activity studies revealed that the effect of vasopressin neuropeptides on social recognition resides in the 5-8 part of the AVP molecule. The peptide (pGlu4,Cyt6) AVP-(4-8) was more potent than DGAVP in this behavioral paradigm. These effects bear similarities with the memory enhancing effects of vasopressin neuropeptides as found in other test procedures.

Animals↗

PubMed1990

Naltrexone attenuates self-injurious behavior in mentally retarded subjects.

The effect of naltrexone on the frequency of self-injurious behavior (SIB) was investigated in 6 male subjects with profound mental retardation. Following a double-blind placebo-controlled crossover design, naltrexone was administered in a dose of 50 mg once daily for 3 consecutive weeks. In 2 of 5 subjects, a significant decrease of SIB frequency could be demonstrated, and in 1, a tendency to a reduction was found. No effect on duration of restrain time was found in 3 subjects. These data suggest that disturbances of the endogenous opioid systems may be involved in the pathophysiology of SIB of certain patients.

Administration, Oral↗

PubMed1990

Chronic pretreatment with naltrexone facilitates acquisition of intravenous cocaine self-administration in rats.

Opioid systems may be involved in the reinforcing effects of drugs of abuse. It has been shown that the opioid antagonist naltrexone attenuates acquisition of intravenous cocaine self-administration behaviour in rats. Using a similar experimental set-up the effect of chronic blockade of opioid systems prior to cocaine exposure was examined. Rats were tested for acquisition of self-administration of one of 3 graded unit doses of cocaine (0.08, 0.16 and 0.32 mg.kg-1 per infusion) or saline. Chronic pretreatment with naltrexone (10 mg.kg-1 per day for 12 days) enhanced acquisition of intravenous cocaine self-administration but only in rats tested with the medium cocaine unit dose. It is concluded that chronic blockade of opioid systems facilitates acquisition of cocaine self-administration, probably by enhancing the reinforcing effect of cocaine.

Animals↗

PubMed1990

A single injection of a biodegradable microsphere formulation of the ACTH-(4-9) analogue ORG 2766 accelerates functional recovery after brain damage.

The functional recovery from impaired motor activity induced by 6-hydroxydopamine lesions in rat nucleus accumbens was accelerated by subcutaneous treatment with the ACTH-(4-9) analogue Met/O2/-Glu-His-Phe-D-Lys-Phe (ORG 2766). Treatment was effective after daily injections of ORG 2766 dissolved in saline during the first 6 days following the lesion (ED50: 28.5 ng kg-1 day-1) or after a single injection of the peptide in a biodegradable microsphere formulation administered after the lesion (ED50: 8.9 ng kg-1 day-1). This study shows that a single injection of a microsphere preparation can replace multiple injections with ORG 2766 in order to facilitate functional recovery after brain damage.

Adrenocorticotropic Hormone↗

PubMed1990