PubMed Health⌕ Search

Biomedical subjects

Jan M Van Ree

Publications and source records attributed to Jan M Van Ree.

18 recordsLinked to original sources
PubMed2006

Effects of frequent cannabis use on hippocampal activity during an associative memory task.

Interest is growing in the neurotoxic potential of cannabis on human brain function. We studied non-acute effects of frequent cannabis use on hippocampus-dependent associative memory, investigated with functional Magnetic Resonance Imaging (fMRI) in 20 frequent cannabis users and 20 non-users matched for age, gender and IQ. Structural changes in the (para)hippocampal region were measured using voxel-based morphometry (VBM). Cannabis users displayed lower activation than non-users in brain regions involved in associative learning, particularly in the (para)hippocampal regions and the right dorsolateral prefrontal cortex, despite normal performance. VBM-analysis of the (para)hippocampal regions revealed no differences in brain tissue composition between cannabis users and non-users. No relation was found between (para)hippocampal tissue composition and the magnitude of brain activity in the (para)hippocampal area. Therefore, lower brain activation may not signify neurocognitive impairment, but could be the expression of a non-cognitive variable related to frequent cannabis use, for example changes in cerebral perfusion or differences in vigilance.

Adult↗
PubMed2006

Anxiety and ethanol consumption in victorious and defeated mice; effect of kappa-opioid receptor activation.

Alcohol consumption and addiction have been related to anxiety and the anxiolytic effect of ethanol. It has been shown in mice that losers with repeated experience of social defeats are more anxious than winners with repeated experience of victories. Mice with a different social status were tested for their oral ethanol consumption using a free two bottle choice paradigm and for their social approach behaviour after ethanol consumption using the partition test, in which anxiety is an important component. In addition, the sensitivity of the animals for the kappa-opioid receptor agonist U-50,488H (2.5 mg/kg, s.c.) was assessed using the partition test, in which this drug has been shown to induce anxiolytic-like effects. Further, the effect of daily treatment with U-50,488H for 8 days on ethanol consumption was tested in animals that had consumed ethanol and were subjected during these 8 days to a period of 5 days of interruption of ethanol supply and subsequently to a period of 3 days of renewed access to ethanol. Losers consumed more ethanol than winners. Consumption of ethanol was accompanied by a decrease of anxiety level, as evidenced by an increased approach behaviour in the partition test. U-50,488H stimulated ethanol consumption after a period of 5 days of interruption of ethanol supply and drug treatment in the losers, but not in the winners. U-50,488H increased approach behaviour in the losers not consuming ethanol and decreased this behaviour in the winners, especially in those that had consumed ethanol. It is postulated that U-50,488H acts as a partial agonist in this respect. The increased anxiety may be related to the enhanced ethanol consumption in the losers, which may be of relevance for the etiology of alcohol addiction.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2006

Long-term effects of frequent cannabis use on working memory and attention: an fMRI study.

RATIONALE: Excessive use of cannabis may have long-term effects on cognitive abilities. Mild impairments have been found in several cognitive domains, particularly in memory and attention. It is not clear, however, whether these effects also occur with moderate, recreational use of cannabis. Furthermore, little is known about underlying brain correlates. OBJECTIVES: The aim of this study is to assess brain function in frequent but relatively moderate cannabis users in the domains of working memory and selective attention. METHODS: Functional magnetic resonance imaging was used to examine verbal working memory and visuo-auditory selective attention in ten frequent cannabis users (after 1 week of abstinence) and ten non-using healthy controls. Groups were similar in age, gender and estimated IQ. RESULTS: Cannabis users and controls performed equally well during the working memory task and the selective attention task. Furthermore, cannabis users did not differ from controls in terms of overall patterns of brain activity in the regions involved in these cognitive functions. However, for working memory, a more specific region-of-interest analysis showed that, in comparison to the controls, cannabis users displayed a significant alteration in brain activity in the left superior parietal cortex. CONCLUSION: No evidence was found for long-term deficits in working memory and selective attention in frequent cannabis users after 1 week of abstinence. Nonetheless, frequent cannabis use may affect brain function, as indicated by altered neurophysiological dynamics in the left superior parietal cortex during working memory processing.

Adult↗
PubMed2005

Development of pharmaceutical heroin preparations for medical co-prescription to opioid dependent patients.

Presently, there is a considerable interest in heroin-assisted treatment: co-prescription of heroin to certain subgroups of chronic, treatment-resistant, opioid dependent patients. In 2002, nine countries had planned (Australia, Belgium, Canada, France, Spain) or ongoing (Germany, The Netherlands, Switzerland, United Kingdom) clinical trials on this subject. These trials (and the routine heroin-assisted treatment programs that might result) will need pharmaceutical heroin (diacetylmorphine) to prescribe to the patients. Research into the development of pharmaceutical forms of heroin for prescription to addicts can benefit from the large amount of knowledge that already exists regarding this substance. Therefore, in this paper we review the physicochemical and pharmaceutical properties of diacetylmorphine and the clinically investigated routes of administration, as well as routes of administration utilised on the street in the context of developing pharmaceutical heroin formulations for prescription to addicts. Patient acceptability of the formulation is essential, because heroin-assisted treatment is aimed at treatment-resistant addicts, who often have to be encouraged to participate (or to maintain participation) in a treatment program. This means that the most suitable products would have pharmacokinetic profiles mimicking that of diacetylmorphine for injection, with rapid peak concentrations of diacetylmorphine and 6-acetylmorphine, ensuring the 'rush effect' and the sustained presence of morphine(-6-glucuronide) creating the prolonged euphoria. Diacetylmorphine for inhalation after volatilisation (via 'chasing the dragon') seems to be a suitable candidate, while intranasal and oral diacetylmorphine are currently thought to be unsuitable. However, oral and intranasal delivery systems might be improved and become suitable for use by heroin dependent patients.

Analgesics, Opioid↗
PubMed2005

Decrease of kappa-opioid receptor mRNA level in ventral tegmental area of male mice after repeated experience of aggression.

Brain opioid systems have been implicated in the regulation of social interaction, including agonistic behaviour. kappa-Opioid receptor B and C mRNA levels were decreased in the ventral tegmental area but not in the nucleus accumbens in male mice with repeated experience of social victories (winners), but not in mice after social defeats (losers) after 10 but not 20 days of confrontations. mu-Opioid receptor mRNA levels were not changed.

Aggression↗
PubMed2005

Pharmacokinetic comparison of two methods of heroin smoking: 'chasing the dragon' versus the use of a heating device.

In preparation for a trial on co-prescription of inhalable heroin and methadone, two methods for inhalation of heroin/caffeine tablets were compared: the commonly used method of 'chasing the dragon' and a standardised procedure for inhalation of volatilised heroin, using a heating device. Five male addicts inhaled a tablet of smokable heroin daily for 5 days, alternating the inhalation method. Plasma concentrations of heroin, 6-acetylmorphine, morphine and morphine-3- and -6-glucuronide were determined using a liquid chromatography method with tandem mass spectrometric detection. The exposure to heroin and its metabolites (expressed as areas under the concentration-time curve) was significantly lower after smoking via the heating device than after 'chasing the dragon': heroin 80% and 6-acetylmorphine 73% lower (p < 0.05). Maximal concentrations of heroin and 6-acetylmorphine were also 80% and 70% lower (p < 0.05) after using the heating device. 'Chasing the dragon' is a more efficient inhalation method than inhalation via the heating device.

Administration, Inhalation↗
PubMed2004

Process characterisation, optimisation and validation of production of diacetylmorphine/caffeine sachets: a design of experiments approach.

Powder filled sachets containing a 3:1 (w/w) powder mixture of diacetylmorphine base and caffeine anhydrate were developed as a dosage form for smokable heroin used for the treatment of chronic, treatment-resistant heroin addicts. The powder mixture was filled into sachets using a micro dose auger filler machine. The goal of this study was to identify the most important process variables that influence precision of dosing. Five variables were tested: auger speed, agitator speed, hopper fill level, dose interval, and dose. An experimental design was used to study the effects of each of these variables, including possible non-linear and interaction effects. A 9-term regression model was constructed, explaining 94% of the observed variation in dose weight variation coefficient. Dose, agitator speed and hopper fill level were the most important variables. The regression model was used to identify optimal settings of the variables for four sachet doses intended for routine manufacture. The results of four test batches manufactured with these optimised settings showed that accurate (accuracy: 99.0-101.0%) and precise (CV: 3.2-5.3%) filling of diacetylmorphine/caffeine sachets is possible using the micro dose auger filler machine.

Administration, Inhalation↗
PubMed2004

Neonatal dexamethasone treatment affects social behaviour of rats in later life.

Synthetic glucocorticoids, like dexamethasone (DEX), have been frequently administered to premature infants to prevent chronic lung disease. Major concern has arisen about the long-term neurodevelopmental sequelae of this DEX treatment. In the present study, we found that neonatal DEX treatment in rats, using a treatment protocol resembling the one used in the clinical situation, increased social play behaviour in juvenile life. Furthermore, neonatal DEX treatment increased sexual motivation and intromission behaviour in the bi-level chamber, decreased submissive behaviour during an aggressive encounter, and impaired social memory in adulthood. These changes in social behaviour are not due to a general behavioural impairment since anxiety behaviour in the elevated plus maze and exploratory activity in the open-field were not affected in DEX rats. In addition, DEX rats showed no alteration in the total duration of social interest or social activity during a social interaction test. These effects of neonatal DEX treatment on behaviour later in life likely result from neurodevelopmental actions of the hormone since we found no differences in received maternal care between DEX and SAL treated pups. Together these results indicate that neonatal treatment with DEX selectively alters aspects of the behavioural response to social challenges. Thus, neonatal DEX treatment may lead to inappropriate interactions with conspecifics later in life. These data therefore warrant investigation of lasting and potentially adverse effects of treatment of human neonates with DEX on social functioning.

Agonistic Behavior↗
PubMed2004

Modulation of anxiety-related behaviors by mu- and kappa-opioid receptor agonists depends on the social status of mice.

This study was aimed to determine the effects of mu- and kappa-opioid receptor activation in relation to the social status of mice, being a winner with repeated experience of victories or a loser with repeated experience of social defeats. The behaviors of the animals were assessed in a social encounter test measuring the communicative behavior towards a familiar and an unfamiliar partner behind a perforated transparent partition (partition test) and in an elevated plus-maze test estimating the anxiety level of mice. Placebo and graded doses of the mu-opioid receptor agonist DAMGO (0.5 and 2 mg/kg s.c.) and the kappa-opioid receptor agonist U-50,488H (0.6, 1.25, and 2.5 mg/kg s.c.) were administered to the control mice, winners and losers in two experiments. In the partition test, the winners spent somewhat more time and the losers less time than the controls in the vicinity of their partner probably related to a lower and higher level of anxiety respectively. In the plus-maze test the losers appeared to have a somewhat higher anxiety level than the controls and winners. In both tests DAMGO produced anxiogenic-like effects in the winners and the controls, but not in the losers. Winners hardly responded to treatment with U-50,488H, while the losers responded dose dependently with an anxiolytic-like effect in both tests. It is concluded that anxiety-like responses in mice are differentially affected by stimulation of mu- and kappa-opioid receptors and that the effects depend on the social status of the animals.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2004

Dissecting complex behaviours in the post-genomic era.

Identifying gene functions in behaviours has so far relied mainly on achievements in the field of molecular genetics. Further progress can be made by developing new approaches that allow refinement of behavioural phenotypes. The current availability of several thousand different mutant mice challenges behavioural neuroscientists to extend their views and methodologies, to dissect complex behaviours into behavioural phenotypes, and subsequently to define gene-behavioural phenotype relationships. Here, we plead for multi-day automated behavioural observations in carefully designed environments.

Animals↗
PubMed2003

Physical and emotional stress have differential effects on preference for saccharine and open field behaviour in rats.

Stress may influence the sensitivity of subjects to rewarding stimuli and stress modality may differentially affect this sensitivity. This relation was investigated in our animal model using chronic physical (repeated mild foot shocks) and emotional (witness) stress. Previous research has established that the two stressors have differential long-term effects on behaviour, where physical stress caused inactivity in a small open field and emotional stress hyperactivity. Rats were stressed on 5 consecutive days and tested for locomotor activity in a small open field (day 10) and saccharine preference (day 11). The preference for graded concentrations of saccharine over water was used as a measure for their sensitivity to reward. Physical stress treatment induced a long-term decrease both in preference for saccharine and open field activity compared to control treatment. Emotional stress animals showed an increase in open field behaviour activity and a slight increase in saccharine preference. Physical stress seems to cause anhedonia, while emotional stress might cause an increased sensitivity to reward. In conclusion, stress can induce differential long-term effects on sensitivity to positive stimuli and the response to novelty depending on stress modality.

Adaptation, Psychological↗
PubMed2003

Neonatal lesions in the amygdala or ventral hippocampus disrupt prepulse inhibition of the acoustic startle response; implications for an animal model of neurodevelopmental disorders like schizophrenia.

Prepulse inhibition of the acoustic startle response is a behavioural tool applied to assess sensorimotor gating processes in humans and rats. Schizophrenic patients show deficits in prepulse inhibition of the acoustic startle response. The animal model of neurodevelopmental disorders such as schizophrenia, as purported in earlier reports and the present study, is based on the assumption that damage to brain structures early in life (on day 7) disrupts brain maturation of structures connected to the damaged areas, measurable by behavioural changes, whereas similar damage later in life (on day 21) does not result in these behavioural changes. Locomotor activity, the acoustic startle response and its prepulse inhibition were investigated in adult rats lesioned in the amygdala or ventral hippocampus on day 7 or 21 of life. The acoustic startle response was increased in animals lesioned in the amygdala on day 7 or 21 of life, but not in animals lesioned in the ventral hippocampus. Prepulse inhibition was impaired and locomotor activity enhanced in animals lesioned in the amygdala or ventral hippocampus on day 7, but not in animals lesioned in these structures on day 21 of life. The results on the acoustic startle response are suggestive of amygdaloid influences on modulation of the acoustic startle response. The effects of early postnatal lesions on prepulse inhibition and locomotor activity are in support of the animal model of neurodevelopmental disorders like schizophrenia.

Acoustic Stimulation↗
PubMed2003

Receptor-selective changes in mu-, delta- and kappa-opioid receptors after chronic naltrexone treatment in mice.

Chronic treatment with the opioid antagonist naltrexone induces functional supersensitivity to opioid agonists, which may be explained by receptor up-regulation induced by opioid receptor blockade. In the present study, the levels of opioid receptor subtypes through the brain of mice were determined after chronic naltrexone treatment using quantitative in vitro autoradiography. This is the first complete mapping study in mice for micro-, delta- and kappa-opioid receptors after chronic naltrexone exposure. Treatment with naltrexone clearly induced up-regulation of micro- (mean 80%) and, to a lesser extent, delta-opioid receptors (mean 39%). The up-regulation of micro- and delta-opioid receptors was evident throughout the brain, although there was variation in the percentage change across brain regions. In contrast, consistent up-regulation of kappa-opioid receptors was observed in cortical structures only and was not so marked as for micro- and delta-opioid receptors. In noncortical regions kappa-opioid receptor expression was unchanged. Taken together, the present findings suggest opioid receptor subtype-selective regulation by chronic naltrexone treatment in mice.

Animals↗
PubMed2002

The effects of neonatal lesions in the amygdala or ventral hippocampus on social behaviour later in life.

Disruption of normal social behaviour is seen in psychiatric neurodevelopmental disorders like schizophrenia or autism. In a rat model of neurodevelopmental disorders we investigated the social behavioural changes after damage of limbic brain areas, at two early stages of life. The effects of ibotenic acid lesions made on day 7 or 21 of life in the amygdala (AM) ((baso)lateral/medical) or ventral hippocampal area on social play behaviour, social behaviour unrelated to social play behaviour early in life, and social behaviour in adulthood were assessed. Lesions of the AM, but not lesions of the ventral hippocampal area, resulted in decreased social play behaviour, and no differences were found between lesions made on day 7 or 21 of life. Social behaviour unrelated to social play behaviour early in life and in adulthood was decreased in animals lesioned in the AM on day 7 but not in animals lesioned on day 21 of life. This effect was particularly present in animals with an additional lesion in the medial nuclei of the AM. Lesions in the ventral hippocampal area did not affect social behaviour. It is concluded that the AM is an important structure for social play behaviour. The effects on social behaviour that are dependent on the day of lesioning (day 7 vs. 21) are an indication of a neurodevelopmental deficit of structures connected to the (medial part) of the AM.

Aging↗
PubMed2002

Neonatal development of projections to the basolateral amygdala from prefrontal and thalamic structures in rat.

Recently an animal model for neurodevelopmental disorders has been developed. In this model the effects of an early neonatal [postnatal day 7 (Pd7)] basolateral amygdala lesion are compared with the effects of a lesion later in life (Pd21). Early amygdala damage results in enduring behavioral disturbances that become more manifest after puberty. These disturbances were not present in animals lesioned at Pd21. Accordingly it was postulated that the early damage may affect the neuroanatomical and neurochemical organization and functioning of other brain structures. To obtain information on the innervation of the amygdala during normal development, we used the retrograde tracer fluoro-gold. From neonatal day 7 onward (studied until Pd19), retrogradely labeled cells were present in the caudal and rostral thalamus, the substantia innominata, and the prefrontal but not the caudal cortex. Development of the topography of the projecting cells differed substantially for the thalamic regions and substantia innominata vs. the cortical regions. In thalamic regions and substantia innominata, no changes were observed during the studied period (Pd7-Pd9). In the prefrontal cortex, the number of labeled cells increased (from Pd7 to Pd13), the topography of the location of the cells changed from unilateral to bilaminar (from Pd9 to Pd13), and the number of subareas in which the cells were present increased (from Pd7 to Pd13). In the caudal cortex, relatively few cells were present up to Pd15. From Pd17 onward, a bilaminar topography of the location of the cells was observed. These data provide information on the circuitry that may be involved in the aberrant neurodevelopment of neonatally amygdala-lesioned rats, which has been proposed as an animal model for neurodevelopmental psychopathological disorders.

Aging↗
PubMed2002

Amygdala or ventral hippocampal lesions at two early stages of life differentially affect open field behaviour later in life; an animal model of neurodevelopmental psychopathological disorders.

Psychiatric disorders like schizophrenia or autism are thought to result from disruption of the normal pattern of brain development. Abnormalities in the amygdaloid complex and hippocampus have been reported in these disorders. In the present study rats were lesioned in the amygdala or ventral hippocampus on day 7 of life (immature brain) or day 21 of life (almost mature brain) and open field behaviour was determined later in life before and after puberty. Lesioning on day 7 resulted in behavioural changes, interpreted as locomotor stereotypy and decreased anxiety in case of amygdala or hippocampus, respectively. These effects were more profoundly present after puberty. Lesioning on day 21 did not result in these behavioural changes, which subscribes to the importance of the stage of brain maturation on functional development. The results suggest that the behavioural changes in rats lesioned on day 7 may due to a malfunctioning of structures connected to the amygdala or ventral hippocampus. Brain lesions made on day 7 of life may serve as a potential model of psychopathological neurodevelopmental disorders.

Aging↗
PubMedDate not supplied

Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride.

A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to 150 mg/mL with water for injection before use. Addition of bulking agents for improvement of the cake structure of the lyophilised product appeared unnecessary. Stability studies indicated good stability of the lyophilised product under prescribed storage conditions (25 degrees C, 60% relative humidity) and under more extreme conditions (40 degrees C, 75% relative humidity). The reconstituted product was found to be stable for six days at room temperature. Suitability of the product for multiple use was supported by the fact that the reconstituted product was found to be antimicrobially active.

Chemistry, Pharmaceutical↗