Twenty years of human research ethics committees in the Baltic States.

Two decades have passed since the first attempts were made to establish systematic ethical review of human research in the Baltic States. Legally and institutionally much has changed. In this paper we provide an historical and structural overview of ethical review of human research and identify some problems related to the role of ethical review in establishing quality research environment in these countries. Problems connected to (a) public availability of information, (b) management of conflicts of interest, (c) REC composition and motivation of REC members, and (d) differing levels of stringency of ethical review for different types of studies, are identified. Recommendations are made to strengthen cooperation among the Baltic RECs.

Targeted invalidation of CCK2 receptor gene induces anxiolytic-like action in light-dark exploration, but not in fear conditioning test.

RATIONALE: Evidence suggests that gamma-aminobutyric acid (GABA) and cholecystokinin (CCK) have opposite roles in the regulation of anxiety. OBJECTIVES: The aim of our work was to study the behaviour of CCK(2) receptor deficient mice in light-dark exploration and fear conditioning tests. Moreover, the action of diazepam and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), having the opposite effect on GABA(A) receptors, was evaluated on the exploratory behaviour in these mice. Expression levels of GABA(A) receptor subunit genes were also measured. METHODS: Light-dark exploration and fear conditioning tests were used to determine changes in anxiety of mice. The action of diazepam (0.5-2 mg/kg i.p.) and DMCM (0.25-1 mg/kg i.p.) was studied in the light-dark box. The effect of DMCM was also evaluated in the motor activity test to demonstrate that its anti-exploratory action was not related to motor suppression. Expression levels of GABA(A) receptor subunit genes were determined by means of real-time polymerase chain reaction (qRT-PCR). RESULTS: Female mice lacking CCK(2) receptors displayed increased exploratory activity in the light-dark box compared to their wild-type (+/+) littermates. Locomotor activity in the motility boxes and the intensity of freezing did not differ in wild-type (+/+) and homozygous (-/-) mice. Treatment with diazepam (0.5 mg/kg) increased the number of transitions in wild-type (+/+) animals, whereas in homozygous (-/-) mice diazepam (0.5-2 mg/kg) reduced exploratory activity. Administration of DMCM (0.25-1 mg/kg) induced an anxiogenic-like effect in homozygous (-/-) mice, but did not change their locomotor activity. Gene expression analysis established a 1.6-fold increase in the expression of the alpha2 subunit of GABA(A) receptors in the frontal cortex of homozygous (-/-) mice. CONCLUSION: Genetic invalidation of CCK(2) receptors induced an anxiolytic-like action in exploratory, but not in conditioned models of anxiety. The observed reduction in anxiety in homozygous (-/-) mice is probably related to an increased function of GABAergic system in the brain.

Role of CCK in anti-exploratory action of paroxetine, 5-HT reuptake inhibitor.

The administration of paroxetine (0.5-8 mg/kg), a selective 5-HT reuptake inhibitor, induced a dose-dependent reduction of exploratory activity of rats in the motility test. In the elevated plus-maze paroxetine was less effective, only 8 mg/kg of paroxetine decreased the exploratory behaviour of rats. The doses of paroxetine (2-8 mg/kg) reducing the exploratory activity in the motility test increased the density of CCK receptors in the frontal cortex, but not in the hippocampus. The treatment of rats with the CCK(B) receptor antagonist LY288,513 (0.01-1 mg/kg) did not change the exploratory activity. However, the reduction of exploratory activity induced by the low dose of paroxetine (2 mg/kg), but not by the higher dose (8 mg/kg), was dose-dependently reversed by the administration of LY288,513. Moreover, LY288,513 did not affect the anti-exploratory action of paroxetine (8 mg/kg) in the elevated plus-maze. Diazepam at doses (0.5-1.0 mg/kg) not suppressing the locomotor activity did not change the anti-exploratory action of paroxetine in the motility test. It is likely that the anti-exploratory action of a low dose of paroxetine (2 mg/kg) is not related to the increase in anxiety, but rather to the reduction of exploratory drive. Evidence exists that this effect of paroxetine is mediated via the activation of CCK-ergic transmission.