| First Author | Raud S | Year | 2005 |
| Journal | Psychopharmacology (Berl) | Volume | 181 |
| Issue | 2 | Pages | 347-57 |
| PubMed ID | 15830228 | Mgi Jnum | J:114297 |
| Mgi Id | MGI:3688709 | Doi | 10.1007/s00213-005-2255-x |
| Citation | Raud S, et al. (2005) Targeted invalidation of CCK2 receptor gene induces anxiolytic-like action in light-dark exploration, but not in fear conditioning test. Psychopharmacology (Berl) 181(2):347-57 |
| abstractText | 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. |
