Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery.

Clenbuterol is a ß2 -adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg(-1) day(-1) ) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po ) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P < 0.05). The fit of muscle contraction and relaxation force kinetics indicated that clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P < 0.05), and only the fast rate constant of relaxation in soleus muscle (P < 0.05). Myofibrillar ATPase activity increased in both relaxed and activated conditions in soleus (P < 0.001), suggesting that the depressed specific tension was not due to the myosin head alteration itself. Moreover, action potential-elicited Ca(2+) transients in flexor digitorum brevis fibres (fast twitch fibres) from clenbuterol-treated animals demonstrated decreased amplitude after 14 days (-19%, P < 0.01) and 21 days (-25%, P < 0.01). In conclusion, we showed that chronic clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca(2+) release during contraction could partially explain these deleterious effects.

Emotional experience and estimates of D2 receptor occupancy in psychotic patients treated with haloperidol, risperidone, or olanzapine: an experience sampling study.

OBJECTIVE: Blockade of dopamine D(2) receptors is thought to mediate the therapeutic effects of antipsychotic medication but may also induce social indifference. As antipsychotic drugs differ in D(2) receptor binding, "tight" and "loose" binding drugs may be hypothesized to differentially affect emotional experience. The present study investigates the differential effects of relatively tight versus looser binding drugs on the experience of emotions in the realm of daily life. METHOD: We assessed positive and negative affect in the daily life of 109 patients with a DSM-IV diagnosis of psychotic disorder who were currently taking antipsychotic medication by using the experience sampling method (a structured diary technique). Antipsychotic medication was classified as loose (olanzapine; n = 35) or tight (haloperidol, risperidone; n = 74) binding, based on the drug's dissociation constants at the D(2) receptor. The study was conducted from 2007 to 2008. RESULTS: Multilevel analyses showed a significant interaction between binding group (loose vs tight) and D(2) receptor occupancy estimates with regard to the experience of positive (P = .008) and negative (P = .019) affect. For tight-binding-agent users, a significant association was found between D(2) receptor binding estimates and both positive affect (P = .040) and negative affect (P = .0001) in the flow of daily life, with increasing levels of estimated D(2) receptor occupancy being associated with decreased feelings of positive affect and increased feelings of negative affect. For loose-binding-agent users, no such association was apparent. These associations were only partly mediated by clinical symptoms. CONCLUSIONS: These findings add ecological validity to previous laboratory findings showing an association between D(2) receptor occupancy and emotional experience.