RATIONALE: Maternal deprivation can result in long-term impairment of neuronal functions and in the development of long-lasting behavioural disorders. OBJECTIVES: This study analysed the effects of a selective cholecystokinin-2 (CCK2) antagonist, 3R-(+)-N-(2,3-dihydro-1methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3yl)-N'-(3-methyl phenyl) urea (L365,260), in anxiety- and stress-related behaviours of adult rats that were deprived (D) from their mother and littermates for 3 h everyday during 14 days after birth. METHODS: The behaviour was studied in actimeter, in open field and after food and water deprivation. Corticosterone plasma levels were quantified after food and water deprivation. The effects of L365,260 were studied in the behavioural changes observed in D rats. RESULTS: No differences in circadian motor activity between non-deprived (ND) and D rats were observed. D rats showed a 50% decrease in their number of visits to the central (aversive) part of the open field compared to ND rats. This effect was suppressed by L365,260. After 20 h of food and water deprivation, an increase in plasma corticosterone was observed in D and ND rats. However, the raise of corticosterone secretion in D rats was dramatically increased (300%) compared to ND rats, indicating a hypersensitised state revealed by this stressful situation. Consumption of sucrose solution (1%) was higher for D rats than for ND rats after food and water deprivation. Sucrose consumption returned to control values following L365,260 treatment. CONCLUSIONS: These results suggest that maternal deprivation led to an increase in anxiety and stress reactivity in adulthood. We propose that these long-lasting changes are partly dependent on CCKergic transmission involving the activation of CCK2 receptors.
RATIONALE: Maternal deprivation can result in long-term impairment of neuronal functions and in the development of long-lasting behavioural disorders. OBJECTIVES: This study analysed the effects of a selective cholecystokinin-2 (CCK2) antagonist, 3R-(+)-N-(2,3-dihydro-1methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3yl)-N'-(3-methyl phenyl) urea (L365,260), in anxiety- and stress-related behaviours of adult rats that were deprived (D) from their mother and littermates for 3 h everyday during 14 days after birth. METHODS: The behaviour was studied in actimeter, in open field and after food and water deprivation. Corticosterone plasma levels were quantified after food and water deprivation. The effects of L365,260 were studied in the behavioural changes observed in D rats. RESULTS: No differences in circadian motor activity between non-deprived (ND) and D rats were observed. D rats showed a 50% decrease in their number of visits to the central (aversive) part of the open field compared to ND rats. This effect was suppressed by L365,260. After 20 h of food and water deprivation, an increase in plasma corticosterone was observed in D and ND rats. However, the raise of corticosterone secretion in D rats was dramatically increased (300%) compared to ND rats, indicating a hypersensitised state revealed by this stressful situation. Consumption of sucrose solution (1%) was higher for D rats than for ND rats after food and water deprivation. Sucrose consumption returned to control values following L365,260 treatment. CONCLUSIONS: These results suggest that maternal deprivation led to an increase in anxiety and stress reactivity in adulthood. We propose that these long-lasting changes are partly dependent on CCKergic transmission involving the activation of CCK2 receptors.
Authors: M G Bock; R M DiPardo; B E Evans; K E Rittle; W L Whitter; D E Veber; P S Anderson; R M Freidinger Journal: J Med Chem Date: 1989-01 Impact factor: 7.446