Sweet taste pleasantness is modulated by morphine and naltrexone

Rodent models highlight the key role of µ-opioid receptor (MOR) signaling in palatable food consumption. In humans however, the effects of MOR stimulation on eating and food liking remain unclear. In a bidirectional psychopharmacological cross-over study, 49 healthy men underwent a sweet taste paradigm following double-blind administration of the MOR agonist morphine, placebo, and the opioid antagonist nalt rexone. We hypothesized that behaviors regulated by the endogenous MOR system would be enhanced by MOR agonism, and decreased by antagonism. The strongest drug effects were expected for the sweetest (high-calorie) sucrose solution, as reported in rodents. However, very sweet sucrose-water solutions are considered sickly and aversive by many people (called sweet dislikers). Since both sweet likers and dislikers were tested, we were able to assess whether MOR manipulations affect pleasantness ratings differently depending on both subjective and objective value. As hypothesized, MOR stimulation with morphine increased pleasantness of the sweetest of five sucrose solutions, without enhancing pleasantness of the lower-sucrose solutions. For opioid antagonism, an opposite pattern was observed for the sweetest drink only. This bidirectional effect of agonist and antagonist treatment is consistent with rodent findings that MOR manipulations most strongly affect the highest-calorie foods. Importantly, the observed drug effects on pleasantness of the sweetest drink did not differ between sweet likers and dislikers. We speculate that the MOR system promotes survival in part by increasing concordance between the objective (caloric) and subjective (hedonic) value of food stimuli, so that feeding behaviour becomes more focused on the richest food available

Heroin versus cocaine: opposite choice as a function of context but not of drug history in the rat

Rationale Previous studies have shown that rats trained to self-administer heroin and cocaine exhibit opposite preferences, as a function of setting, when tested in a choice paradigm. Rats tested at home prefer heroin to cocaine whereas rats tested outside the home prefer cocaine to heroin. Here we investigated whether drug history would influence subsequent drug preference in distinct settings. Based on a theoretical model of drug-setting interaction, we predicted that regardless of drug history rats would prefer heroin at home and cocaine outside the home. Methods Rats with double-lumen catheters were first trained to self-administer either heroin (25 μg/kg) or cocaine (400 μg/kg) for 12 consecutive sessions. Twenty-six rats were housed in the self-administration chambers (thus, they were tested at home) whereas 30 rats lived in distinct home cages and were transferred to self-administration chambers only for the self-administration session (thus, they were tested outside the home). The rats were then allowed to choose repeatedly between heroin and cocaine within the same session for 7 sessions. Results Regardless of the training drug, the rats tested outside the home preferred cocaine to heroin whereas the rats tested at home preferred heroin to cocaine. There was no correlation between drug preference and drug intake during the training phase. Conclusion Drug preferences were powerfully influenced by the setting but, quite surprisingly, not by drug history. This suggests that, under certain conditions, associative learning processes and drug-induced neuroplastic adaptations play a minor role in shaping individual preferences for one drug or the other

The Effect of Sugar-Free Versus Sugar-Sweetened Beverages on Satiety, Liking and Wanting: An 18 Month Randomized Double-Blind Trial in Children

BACKGROUND: Substituting sugar-free for sugar-sweetened beverages reduces weight gain. A possible explanation is that sugar-containing and sugar-free beverages cause the same degree of satiety. However, this has not been tested in long-term trials. METHODS: We randomized 203 children aged 7-11 years to receive 250 mL per day of an artificially sweetened sugar-free beverage or a similarly looking and tasting sugar-sweetened beverage. We measured satiety on a 5-point scale by questionnaire at 0, 6, 12 and 18 months. We calculated the change in satiety from before intake to 1 minute after intake and 15 minutes after intake. We then calculated the odds ratio that satiety increased by 1 point in the sugar-group versus the sugar-free group. We also investigated how much the children liked and wanted the beverages. RESULTS: 146 children or 72% completed the study. We found no statistically significant difference in satiety between the sugar-free and sugar-sweetened group; the adjusted odds ratio for a 1 point increase in satiety in the sugar group versus the sugar-free group was 0.77 at 1 minute (95% confidence interval, 0.46 to 1.29), and 1.44 at 15 minutes after intake (95% CI, 0.86 to 2.40). The sugar-group liked and wanted their beverage slightly more than the sugar-free group, adjusted odds ratio 1.63 (95% CI 1.05 to 2.54) and 1.65 (95% CI 1.07 to 2.55), respectively. CONCLUSIONS: Sugar-sweetened and sugar-free beverages produced similar satiety. Therefore when children are given sugar-free instead of sugar-containing drinks they might not make up the missing calories from other sources. This may explain our previous observation that children in the sugar-free group accumulated less body fat than those in the sugar group.<br /

The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward

Differentiation-Induced Remodelling of Store-Operated Calcium Entry Is Independent of Neuronal or Glial Phenotype but Modulated by Cellular Context

Neurogenesis is a complex process leading to the generation of neuronal networks and glial cell types from stem cells or intermediate progenitors. Mapping subcellular and molecular changes accompanying the switch from proliferation to differentiation is vital for developing therapeutic targets for neurological diseases. Neuronal (N-type) and glial (S-type) phenotypes within the SH-SY5Y neuroblastoma cell line have distinct differentiation responses to 9-cis-retinoic acid (9cRA). In both cell phenotypes, these were accompanied at the single cell level by an uncoupling of Ca2+ store release from store-operated Ca2+ entry (SOCE), mediated by changes in the expression of calcium release-activated calcium pore proteins. This remodelling of calcium signalling was moderated by the predominant cell phenotype within the population. N- and S-type cells differed markedly in their phenotypic stability after withdrawal of the differentiation inducer, with the phenotypic stability of S-type cells, both morphologically and with respect to SOCE properties, in marked contrast to the lability of the N-type phenotype. Furthermore, the SOCE response of I-type cells, a presumed precursor to both N- and S-type cells, varied markedly in different cell environments. These results demonstrate the unique biology of neuronal and glial derivatives of common precursors and suggest that direct or indirect interactions between cell types are vital components of neurogenesis that need to be considered in experimental models.</p

Developmental Expression of Kv Potassium Channels at the Axon Initial Segment of Cultured Hippocampal Neurons

Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation

P2 nucleotide receptors on C2C12 satellite cells

In developing muscle cells environmental stimuli transmitted by purines binding to the specific receptors are crucial proliferation regulators. C2C12 myoblasts express numerous purinergic receptors representing both main classes: P2X and P2Y. Among P2Y receptors we have found the expression of P2Y1, P2Y2, P2Y4, P2Y6 and P2Y12 family members while among P2X receptors P2X4, P2X5 and P2X7 were discovered. We have been able to show that activation of those receptors is responsible for ERK class kinase activity, responsible for regulation of cell proliferation pathway. We have also demonstrated that this activity is calcium dependent suggesting Ca2+ ions as secondary messenger between receptor and kinase regulatory system. More specifically, we do suspect that in C2C12 myoblasts calcium channels of P2X receptors, particularly P2X5 play the main role in proliferation regulation. In further development of myoblasts into myotubes, when proliferation is gradually inhibited, the pattern of P2 receptors is changed. This phenomenon is followed by diminishing of the P2Y2-dependent Ca2+ signaling, while the mRNA expression of P2Y2 receptor reminds still on the high level. Moreover, P2X2 receptor mRNA, absent in myoblasts appears in myotubes. These data show that differentiation of C2C12 cell line satellite myoblasts is accompanied by changes in P2 receptors expression pattern

Temporal and effort cost decision-making in healthy individuals with subclinical psychotic symptoms

The value people attribute to rewards is influenced both by the time and the effort required to obtain them. Impairments in these computations are described in patients with schizophrenia and appear associated with negative symptom severity. This study investigated whether deficits in temporal and effort cost computations can be observed in individuals with subclinical psychotic symptoms (PS) to determine if this dysfunction is already present in a potentially pre-psychotic period. Sixty participants, divided into three groups based on the severity of PS (high, medium and low), performed two temporal discounting tasks with food and money and a concurrent schedule task, in which the effort to obtain food increased over time. We observed that in high PS participants the discounting rate appeared linear and flatter than that exhibited by participants with medium and low PS, especially with food. In the concurrent task, compared to those with low PS, participants with high PS exerted tendentially less effort to obtain snacks only when the required effort was high. Participants exerting less effort in the higher effort condition were those with higher negative symptoms. These results suggest that aberrant temporal and effort cost computations might be present in individuals with subclinical PS and therefore could represent a vulnerability marker for psychosis