Association of plasma calcium concentrations with alcohol craving: New data on potential pathways.

Recently, calcium was suggested to be the active moiety of acamprosate. We examined plasma calcium concentrations in association with severity of alcohol dependence and its interaction with regulating pathways and alcohol craving in alcohol-dependent patients. 47 inpatient alcohol-dependent patients undergoing detoxification treatment underwent laboratory testing, including calcium, sodium, liver enzymes as well as serum concentrations of calcitonin, parathyroid hormone and vitamin D. The psychometric dimension of craving was analyzed with the Obsessive Compulsive Drinking Scale (OCDS). The severity of withdrawal was measured with the Alcohol Dependence Scale (ADS) and with the Alcohol Dependence Scale for high-risk sample (ADS-HR). The main findings of our investigation are: a) a negative correlation of plasma calcium concentrations with alcohol craving in different dimensions of the OCDS; b) a negative correlation of plasma calcium concentrations with breath alcohol concentration; c) lowered calcitonin concentration in the high-risk sample of alcoholics; d) lowered plasma vitamin D concentrations in all alcoholic subjects. Our study adds further support for lowered plasma calcium concentrations in patients with high alcohol intake and especially in patients with increased craving as a risk factor for relapse. Lowered calcitonin concentrations in the high-risk sample and lowered vitamin D concentrations may mediate these effects. Calcium supplementation could be a useful intervention for decreasing craving and relapse in alcohol-dependent subjects.

Adolescent peer-rejection persistently alters pain perception and CB1 receptor expression in female rats.

Peer-interactions are particularly important during adolescence and teenagers display enhanced sensitivity toward rejection by peers. Social rejection has been shown to induce alterations in pain perception in humans. However, the neurobiological consequences of adolescent social rejection have yet to be extensively characterized, and no appropriate animal model is available. Here, we propose inadequate playful interactions in adolescent rats as a novel animal model for social peer-rejection and examine potential long-term consequences into adulthood. Acute social pairing of female adolescent Wistar rats with an age-matched rat from the less playful Fischer344 strain was found to alter social play and decrease pain reactivity, indicating Fischer rats as inadequate social partners for Wistar animals. Therefore, in a second experiment, adolescent female Wistar rats were either reared with another Wistar rat (adequate social rearing; control) or with a Fischer rat (inadequate social rearing; play-deprived). Beginning on day 50, all Wistar rats were group housed with same-strain partners and tested for behavioral, neurobiological and endocrine differences in adulthood. Playful peer-interactions were decreased during adolescence in play-deprived animals, without affecting social contact behavior. Consequently, adult play-deprived rats showed decreased pain sensitivity and increased startle reactivity compared to controls, but did not differ in activity, anxiety-related behavior or social interaction. Both groups also differed in their endocrine stress-response, and expression levels of the cannabinoid CB1 receptor were increased in the thalamus, whereas FAAH levels were decreased in the amygdala. The present animal model therefore represents a novel approach to assess the long-term consequences of peer-rejection during adolescence.

Sensorimotor gating, working and social memory deficits in mice with reduced expression of the vesicular glutamate transporter VGLUT1.

Glutamate is the main excitatory neurotransmitter in the central nervous system. A hypoglutamatergic state is believed to play an important role in the pathophysiology of schizophrenia. The release of glutamate in the brain is modulated by a class of vesicular glutamate transporters, VGLUT1-3. Among them, VGLUT1 represents the isoform predominantly expressed in the neocortex and hippocampus. Here we investigated the potential involvement of VGLUT1 deficiency in generating schizophrenia-like abnormalities by testing mice with diminished expression of VGLUT1 in several behavioural tests relevant for schizophrenia. We found behavioural alterations in these mice resembling correlates of schizophrenia, such as working- and social memory impairments and deficits in prepulse inhibition (PPI) of the acoustic startle reflex (ASR), but normal locomotor behaviour under basal conditions. Our data may be important for a better understanding of the contribution of reduced VGLUT1-mediated presynaptic glutamatergic neurotransmission in the generation of several behavioural abnormalities associated with schizophrenia.

Stress triggers anhedonia in rats bred for learned helplessness.

Congenitally helpless (cLH) rats, a well-accepted model for depression, show reduced consumption of sweet solutions only under single-housing conditions, indicating anhedonia under stress. We investigated if anhedonic-like behaviour, measured by a reduction of sweetened-condensed milk (SCM) intake and the pleasure-attenuated startle response (PAS), could be induced by an electric foot-shock stress challenge in group-housed rats. After foot-shock stress, reduced SCM intake was observed in cLH rats compared to non-helpless (cNLH) rats. Furthermore, cLH rats also showed a decreased PAS, indicating deficient reward perception. In summary, we demonstrate that a predisposition for learned helplessness interacts with stress to trigger anhedonic-like behaviour in cLH rats. These findings further add to the validity of congenitally learned helplessness as an animal model of depression, since gene-environment interactions are considered to play a role in the etiology of this disorder.

Chronic intake of fermented floral nectar by wild treeshrews.

For humans alcohol consumption often has devastating consequences. Wild mammals may also be behaviorally and physiologically challenged by alcohol in their food. Here, we provide a detailed account of chronic alcohol intake by mammals as part of a coevolved relationship with a plant. We discovered that seven mammalian species in a West Malaysian rainforest consume alcoholic nectar daily from flower buds of the bertam palm (Eugeissona tristis), which they pollinate. The 3.8% maximum alcohol concentration (mean: 0.6%; median: 0.5%) that we recorded is among the highest ever reported in a natural food. Nectar high in alcohol is facilitated by specialized flower buds that harbor a fermenting yeast community, including several species new to science. Pentailed treeshrews (Ptilocercus lowii) frequently consume alcohol doses from the inflorescences that would intoxicate humans. Yet, the flower-visiting mammals showed no signs of intoxication. Analysis of an alcohol metabolite (ethyl glucuronide) in their hair yielded concentrations higher than those in humans with similarly high alcohol intake. The pentailed treeshrew is considered a living model for extinct mammals representing the stock from which all extinct and living treeshrews and primates radiated. Therefore, we hypothesize that moderate to high alcohol intake was present early on in the evolution of these closely related lineages. It is yet unclear to what extent treeshrews benefit from ingested alcohol per se and how they mitigate the risk of continuous high blood alcohol concentrations.

Appetitive odor-cue conditioning attenuates the acoustic startle response in rats.

We here show that a neutral odor previously paired with a positive emotional context is an effective stimulus for attenuating the acoustic startle response (ASR) in rats. Olfactory cues can, therefore, be effectively used in the startle probe procedure for appetitive conditioning. This cue-induced reduction in ASR is not related to attentional alterations or a more general arousal by odor presentation, the conditioned olfactory cue rather elicits a pleasant emotional state during which the ASR is inhibited. This odor conditioned "pleasure" attenuation of the startle response might, therefore, provide a new effective operational measure for the hedonic aspects of reward.