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In the past, Acetaldehyde (ACD), the main metabolite of ethanol (ETOH), was mainly studied for its toxic and adverse effects (1). However, recently, ACD was reported to determine behavioural and neurochemical effects, following ETOH assumption in rodents (2, 3). Indeed, ACD enhances dopamine levels in nucleus accumbens, stimulates beta-endorphin release from hypothalamic cells, mediating alcohol reinforcing effects (4). Since little is known about the effects of ACD on other central neuropeptides, in this research we aimed to investigate ACD influence on hypothalamic corticotropin-releasing factor (CRF) release. In order to ascertain this hypothesis, different doses of ACD (1, 10, 3x10 microM) have been administered in incubated hypothalamic explants and CRF concentration have been detected by a radioimmunoassay. Our results show that, following 20 min of incubation at 37°C, ACD is able to significantly increase hypothalamic CRF release in a dose-dependent manner (p

The correct realization of a pharmacological therapy needs the individuation of the most appropriate drugs for the treatment of the patient's disease. However, even the most effective, and potent and appropriate drugs cannot assure the therapeutic success, if that compound does not reach the site of action. This result can be obtained only if the physician knows the factors that regulate thepharmacokinetic parameters of the used drugs, i.e. absorption, distribution, metabolism, excretion, that regulate the onset velocity, the duration and the intensity of the drug effects. In the lost years, pharmacological interactions, i.e. the possibility that co-administered drugs interfere with each other on the effects, aroused a raising clinical interest. Pharmacological interactions are useful if they augment the therapeutic efficacy of interacting molecules, but they should be avoided if they reduce the therapeutic effects or increase the adverse reactions. The aim of this brief treatment on the clinical significance of pharmacokinetic interactions is to give some useful suggestions for a rational and proper use of pharmacological poly-therapies, on the basis of the pharmacokinetic parameters, in order to promote the patient's health

Central GABAergic and serotoninergic systems interact with one another and are implicated in controlling different behaviours. A gentle early long-lasting handling can prevent the deficits in locomotion and exploration in open field (O.F.) in 3-month-old male rats prenatally exposed to diazepam (DZ). Purpose of this study was to extend the research to older handled rats prenatally exposed to DZ and to assess the activity of 5-HT1A receptors (Rs), evaluating the performance in O.F. at 3 and 18 months of age following 8-OH-DPAT administration. A single daily s.c. injection of DZ (1.5 mg/kg) from gestation day 14 to gestation day 20 induced in aged, but not in young rats, a decrease in total distance travelled (TDT) and in rearing frequency (RF) and an increase of transitions from the periphery to the centre of the arena (CNT) and in the time spent in the centre of the arena (CAT), compared to controls. 8-OH-DPAT (0.150 mg/kg s.c.), given 1 h before testing, increased TDT and decreased RF, CNT and CAT in both vehicle- and DZ-exposed young rats. In aged rats prenatally exposed to DZ, 8-OH-DPAT induced an increase in TDT and a slight decrease in RF, CNT and CAT. These findings indicate that the effects of handling and of 8-OH-DPAT in prenatally DZ-exposed rats are age-dependent and suggest that O.F. test can represent a valid tool to identify the changes in 5-HT1A Rs activity following drug treatment