Cecilie Goodrich

Effect of lithium on reproduction and postnatal growth of mice.

Mating pairs of mice were maintained continuously on drinking water containing 50 mEq/l LiCl and its effects on reproduction and postnatal development were monitored. In mating pairs put on lithium at 6-8 weeks of age, the lithium does not appear to reduce litter size at birth but it does increase postnatal mortality and the length of time between litters, and reduces the total number of litters a mating pair may have. In mating pairs put on lithium at 3 weeks of age, it severely delays postnatal growth and development of all pups in the litter. With the exception of the liver, this delayed growth and development does not appear to affect internal organs as severely as somatic body parts. This delayed growth may be the result of some effect lithium may have on certain hormones such as prolactin, thyroxine and growth hormone.

The effects of the specific uptake inhibitor Lu 10-171 (citalopram) upon brain indoleamine stores in the maturing mouse.

1. The specific 5-HT uptake inhibitor Lu 10-171 (Citalopram) was used to test uptake inhibition and reduced turnover in maturing mouse brain. 2. All ages showed 5-hydroxyindole acetic acid (5-HIAA) elevation indicative of inhibition and reduced turnover. Enzymatic blockade in conjunction with Lu 10-171 supported the evidence for reduced turnover. 3. The significance of early serotonergic maturation is discussed.

Temperature preferences and the effect of changes in serotonin in maturing mice.

Abstract Behavior of maturing mice in a 20 cm long thermal gradient is described. Mean preferred temperatures (T pref ) under standard test conditions ranged from about 29° to 31° in untreated mice aged 3, 7, 10, and 14 days postpartum, which is similar to the temperature maintained in the nest by parent mice. Increased serotonin (5-HT) after injection of the precursor 5-hydroxytryptophan (30 mg/kg) was generally associated with increasted T pref (7 and 10 days) as compared with vehicle injected littermate controls in a double-blind study. Depletion of 5-HT following p-chlorophenylalanine (400 mg/kg) was associated with decreased T pref (3 and 7 days). Relationships with body temperature and thermoregulation are discussed and handling cautions are presented.

Rates of indoleamine synthesis in maturing mouse brain

1. 1. Rates of 5-hydroxytryptamine (5-HT) synthesis in hemispheres and brainstem of maturing mouse brain have been made. Inhibitor methods with precursor assay have been employed. 2. 2. Rates of 5-HT synthesis are higher in neonatal brain than in vitro enzyme analysis might suggest. Changes in synthetic rate are more conservative in the hemispheres. The lowest synthetic rates are generally at 1 week of age. 3. 3. The possible general significance of maturational rate patterns for 5-HT synthesis are discussed.

The maturational onset of the 5-HT mediated head twitch in mice

The effect of elevated brain serotonin (5-hydroxytryptamine, 5-HT) on the head twitch was examined to determine an age of onset in mice for this 5-HT mediated motor activity. Two different treatments were used to elevate 5-HT: 100 mg/kg L-tryptophan with 100 mg/kg pargyline; and 100 mg/kg 5-HTP with 25 mg/kg carbidopa. Mice from ages 14 to 42 days postpartum were examined. Both treatments showed an onset of the head twitch at 15 days. Juvenile mice of 15-18 days appeared to differ in their response to the two treatments. Although 5-HTP and carbidopa stimulated head twitches, 5-HTP alone had a greater stimulatory effect at these ages, while in the other experiment only those animals receiving the combined tryptophan and pargyline treatment showed significant responses.

Thermoregulatory effects of the specific uptake inhibitor citalopram in maturing mice.

The effects of a single 20 mg/kg dose of citalopram (Lu 10-171) were studied in mice aged 1-10 days. Body temperature measured 2 and 24 hr after treatment was decreased in treated animals as compared with saline injected littermate controls. Two hours after treatment, temperature preference in a thermal gradient was unchanged in animals younger than 6 days; however, in animals 6 days or older, temperature preference was increased as compared with littermate controls. Twenty-four hours after treatment, temperature preference was increased in citalopram-treated animals at all ages tested. The results are discussed in relation to nervous system maturation.

The effects of reserpine upon body weight, brain weight and brain indoleamine stores in maturing mice

Abstract 1. 1. Mice of 1 day, 1 week, 2 weeks, and 6 weeks of age have been injected with the amine depletor reserpine and then measured for changes in body weight, brain weight, and indoleamine stores. 2. 2. Immature mice showed a transient loss of brain weight and a long term loss of body weight. 3. 3. Onset of drug action as reflected in the brains 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) stores was slower in 1 day olds than in later ages. 4. 4. Recovery of 5-HT levels was faster in younger mice while recovery of 5-HIAA levels was faster in older animals. 5. 5. It is suggested that 5-HT recovery is related to differences in 5-HT synthesis at various ages and 5-HIAA recovery is related to the maturity of the brains acid transport system.

Pirenperone effects on temperature preference and body temperature in maturing mice

Thermoregulatory effects of the selective 5-HT2 antagonist pirenperone were studied 1 hr after IP injection in mice aged 1, 3, 5, 7 and 10 days postpartum. Compared with vehicle injected littermates, a dose of 0.16 mg/kg decreased temperature preference (T pref) on a thermal gradient at all ages. No significant effects were observed on body temperature (Tb) at any of the ages. An increased dose (0.48 mg/kg) caused no greater effect on T pref and no significant effect on Tb. These results indicate that Tb and T pref are separable on the basis of receptor pharmacology, and are discussed in relation to drug effects on 5-HT2 receptors.

Biochemical and functional effects of fenfluramine in maturing mice

Biochemical and functional effects of a single dose of fenfluramine were studied in maturing mice aged 1 day or 1, 2 or 6 weeks postpartum. 5-HT and 5-HIAA stores in hemispheres and brain stem were significantly reduced at all ages 1 day after the drug injection. In contrast to adult animals which showed continuing reductions in 5-HT and 5-HIAA 4 weeks after the fenfluramine injection, animals at all younger ages returned to normal by 1 week after the injection. Body weight was reduced 2-4 weeks after fenfluramine injection in 1 week old animals; however 2 week animals showed only a small transient reduction during the first week following fenfluramine. No significant effects were found on body temperature or temperature preference. The results are discussed in relation to the effects of various amine depleting agents.

Maturational age affects pirenperone dose-response pattern.

The effects of the 5-HT2 antagonist pirenperone on temperature preference were observed 1 hr after injection in mice aged 3, 5 and 7 days and at doses of 0.16, 0.48 and 1.6 mg/kg body weight. Although all 3 doses produced significant decreases in preferred temperature at 3 days, only the highest dose had significant effects at ages 5 and 7 days. Analysis of the data suggests that the dose-response relationship depends on age in a way that would be consistent with a shift in the dose-response curve with increasing age.