Assessing Knowledge of Pharmacokinetics in an Integrated Medical Curriculum.

Pharmacokinetics is the branch of pharmacology that describes how the body processes drugs. As most physicians will prescribe drugs during their career, knowledge of pharmacokinetics is indispensable for medical students. Students, however, experience pharmacokinetics as difficult, probably due to its abstract and mathematical nature.

Neonatal basolateral amygdala lesions affect monoamine and cannabinoid brain systems in adult rats.

There is evidence for neurodevelopment disturbances in schizophrenia. In rats, a neonatal basolateral amygdala lesion induces behavioural features in adults reminiscent of the symptomatology of schizophrenia. Dopamine plays a key role in the pathogenesis of schizophrenia, and cannabis use has been implicated in the risk for developing schizophrenia.

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.

Cerebral metabolic consequences in the adult brain after neonatal excitotoxic lesions of the amygdala in rats.

In the present study the effects of neonatal excitotoxic lesions of the amygdala or ventral hippocampus on local cerebral glucose utilisation in the adult rat were studied by means of the [14C]2-deoxyglucose autoradiographic method. Our hypothesis was that damage to the brain during early development leads to long-term functional activity changes in brain regions outside the primary lesioned area which might underlie the behavioural deficits observed in animals with neonatal brain damage. Cerebral glucose utilisation in animals with a neonatal amygdala lesion was significantly decreased in the amygdala itself and in several other brain regions.

Neonatal amygdala lesions affect appetitive motivational and consummatory aspects of social behavior in the rat.

In the present study, rats received amygdala lesions (AMX) on either Postnatal Day 7 (PD 7; immature brain) or PD 21 (almost mature brain), and adult social activity was studied after short-term isolation housing. Sham-operated rats demonstrated increased following and approaching behavior after 7 days of isolation compared with after 4 days of isolation, an effect that was absent in AMX-PD 7 and AMX-PD 21 rats. Furthermore, AMX-PD 7 rats, but not AMX-PD 21 rats, displayed a reduction in investigatory behavior after prolonged isolation.

Reinstatement of cocaine-seeking behavior in rats is attenuated following repeated treatment with the opioid receptor antagonist naltrexone.

In the present study we show that the endogenous opioid systems play a modulating role in cocaine-induced reinstatement of drug-seeking behavior in rats. We investigated the effect of blockade of opioid receptors on reinstatement of cocaine-seeking behavior by cocaine priming. Drug-naive rats were allowed to initiate self-administration behavior of cocaine (30 and 60 mug per infusion, i.

Endogenous cannabinoids are not involved in cocaine reinforcement and development of cocaine-induced behavioural sensitization.

The endogenous cannabinoid system is a relatively novel discovered system consisting of cannabinoid CB1 receptors, which are expressed both in the periphery and in the central nervous system, peripheral cannabinoid CB2 receptors and endogenous cannabinoids, which are anandamide and 2-arachidonyl glycerol. The cannabinoid CB1 receptors have recently been implicated in rewarding aspects of not only the cannabinoid drug Delta9-tetrahydrocannabinol (Delta9-THC), but also of other drugs of abuse, including cocaine. The present study was designed to further investigate the role of CB1 receptors in reward-related effects of cocaine.

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.

Mu-opioid receptors are not involved in acute cocaine-induced locomotor activity nor in development of cocaine-induced behavioral sensitization in mice.

Although mu-opioid receptors have been extensively investigated for their role in drug reinforcement, little is known about the contribution of these receptors to the acute and sensitized locomotor response to cocaine. In this study mu-opioid receptor involvement in acute cocaine-induced locomotor activity and in the development of cocaine-induced behavioral sensitization was evaluated using mu-opioid receptor knockout mice and chronic naltrexone (NTX) pretreatment as models. In addition, co-administration of the specific mu-opioid receptor antagonist CTOP with repeated saline or cocaine injections was used to establish the involvement of mu-opioid receptors in sensitization to the locomotor stimulant effects of cocaine.

Neonatal amygdala lesions and juvenile isolation in the rat: differential effects on locomotor and social behavior later in life.

Pervasive developmental disorders such as autism are characterized by deficits in social interaction and communication. Disturbed development of limbic structures such as the amygdala might underlie these deficits. The authors examined the effects of amygdala lesions on Postnatal Day 7 and juvenile isolation (2 weeks of individual housing during Weeks 4 and 5 of life) on rat locomotor and social activity later in life.

Drug dependence and the endogenous opioid system.

The discovery of endogenous opioids has markedly influenced the research on the biology of drug dependence. Evidence has been presented that these brain substances are self-administered by laboratory animals. This finding, among others, has led to the hypothesis that endogenous opioids are involved in reinforcing habits, including dependence on drugs of abuse.

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.

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.

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.