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E E Shillito

Publications and source records attributed to E E Shillito.

15 recordsLinked to original sources

The failure of p-chlorophenylalanine to affect voluntary alcohol consumption in rats.

1 The effects of p-chlorophenylalanine (PCPA) administered orally and intraperitoneally on rat brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content were compared. The depletion of brain 5-HT and 5-HIAA following PCPA (316 mg/kg) injected intraperitoneally every third day was not significantly different from that following the administration of PCPA (316 mg/kg) by stomach tube on eight consecutive days. 2 Rats tested for alcohol preference before, during and after treatment with PCPA on two intraperitoneal dose regimens (either 316 mg/kg then 100 mg/kg four days later or 316 mg/kg three times at intervals of three days) showed no reduction in voluntary alcohol consumption. 3 The results indicated that depletion of brain 5-HT and 5-HIAA is not responsible for the reduction of voluntary alcohol intake which has been reported to follow chronic oral administration of PCPA to the rat (Myers & Veale, 1968). The possibility of a learned aversion to alcohol due to an association with PCPA administration is discussed.

Alcohol Drinking

Influence of age and of testosterone on the response of male rats to parachlorophenylalanine.

1. Castrated male rats and male rats that had been castrated as well as adrenalectomized, showed hypersexual behaviour 24 h after treatment with parachlorophenylalanine (PCPA), as did intact rats.2. A dose of PCPA 100 mg/kg was sufficient to induce mounting behaviour; this dose lowered the cerebral 5-hydroxytryptamine (5-HT) to about 50% in 24 h and further to 40% in 72 hours.3. Groups of juvenile male rats treated chronically with PCPA 100 mg/kg or 50 mg/kg, or with testosterone propionate 1.25 mg, showed hair loss after three weeks of treatment (6 injections), because of increased social interaction.4. Groups of intact male rats 9-11 weeks old given testosterone propionate 1.25 mg subcutaneously, showed mounting behaviour 3-5 h after the injection which was indistinguishable from the behaviour seen 24 h after treatment with PCPA 100 mg/kg. The 5-HT content of the brain was not altered by testosterone.5. The number of rats which showed mounting after PCPA treatment did not change with age, but the younger rats made more mounts in the observation time than rats more than three months old.6. The age of castration (3 weeks or 4 months) did not influence the results.

Adrenalectomy

Sleep produced by clonidine (2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride).

1. The dose of clonidine (given intravenously) required to elicit sleep in the young chick is 1/25th to 1/50th of an equiactive dose of noradrenaline. The approximate ED50 is 0.01 mumol/kg. Phentolamine (10-15 mg/kg, but not 5 mg/kg) antagonizes the action of both clonidine and noradrenaline.2. Intensive treatment with p-chlorophenylalnine (700 mg/kg for 3-4 days) does not prevent the hypnotic effect of clonidine in the chick, although brain 5-HT is reduced to 15% of normal. Neither is natural sleep modified.3. Sleep after clonidine is not affected by methysergide (0.1-1 mumol/kg, i.m.), but prevented by LSD (0.1-0.3 mumol/kg). The effect of LSD is interpreted as a physiological antagonism.4. Clonidine (50 mg/kg) injected intravenously into adult rats causes sleep which is not abolished by phentolamine (5 mg/kg) or by p-chlorophenylalanine in doses which interfere with natural sleep.5. When, per kg body weight, the same dose of clonidine is injected into the lateral cerebral ventricle of rats, sleep ensues in more than half the animals, and persistent eating in about a third; only one of seventeen rats showed no change in behaviour. Eating and sleeping remained unaltered after p-chlorophenylalanine. The actual dose of clonidine injected into the lateral ventricle was 0.037 mumol, amounting to about 0.15 mumol/kg or 15 times the dose required intravenously in the chick. Noradrenaline 0.15 mumol per (intraventricular) injection caused eating but no sleep, whereas higher doses produced ataxia and paresis.6. The work suggests that clonidine does not elicit sleep by an action requiring the integrity of the 5-HT-containing neurones arising in the raphé nuclei, and that its action is not on tryptamine receptors. In the chick, sleep appears to be produced by a central sympathomimetic effect; it is possible, but not certain, that this also holds for the rat.7. The intravenous hypnotic dose of clonidine for the cat is about the same as that for the rat, but injection is not accompanied by signs of peripheral sympathetic stimulation.

Animals

The effect of parachlorophenylalanine on social interaction of male rats.

1. Juvenile male rats treated with parachlorophenylalanine showed hair loss round the head and neck extending down the chest and abdomen.2. Treated isolated rats did not have this loss of hair, while untreated animals living in the same cage as treated rats lost their hair. The loss therefore seems to be caused by increased social behaviour. This consists of a greater frequency of chasing each other, rolling over and social grooming.3. Adult male rats show an increase in mounting after treatment with parachlorophenylalanine, and this change in behaviour was counteracted by treatment with 5-hydroxytryptophan.4. It is concluded that 5-hydroxytryptamine inhibits sexual behaviour in male rats. The increase in social interaction seen in juvenile rats may be the behavioural precursor of adult sexual behaviour.5. Atropine 2.5 mg/kg blocked all forms of social interaction in adult male rats, although other activity was not altered.

5-Hydroxytryptophan

A method for investigating the effects of drugs on the exploratory behaviour of mice.

1. Exploratory behaviour in mice was observed when they were put on a wooden board to which twelve tunnels were fixed. The number of different tunnels entered (indicating exploration) and the total entries into tunnels were recorded over 5 min on 2 successive days.2. Untreated mice entered more different tunnels in the first minute on the second day on the tunnel board, and this difference in behaviour was taken as an indication that exploration had occurred on the first day. When the behaviour of the treated mice on the second day was similar to that of inexperienced mice on the first day it was inferred that drug treatment had adversely affected exploration.3. Haloperidol 4 mg/kg, chlorpromazine 8 mg/kg and thioridazine 16 mg/kg adversely affected exploration at doses which almost immobilized the mice.4. Amphetamine at 8 mg/kg disrupted exploratory behaviour in the mice, although the mice were observed to move round the board very quickly.5. With tranylcypromine 2 mg and nialamide 100 mg, increased exploratory behaviour by comparison with controls was recorded in the mice when they were tested 24 h after drug treatment.6. Imipramine at 20 mg/kg reduced the total number of tunnels entered by the mice on the first day, but on the second day the mice behaved in a similar way to mice treated with monoamine oxidase inhibitors.

Amphetamine

The effect of parachlorophenylalanine on the behaviour of cats.

1. Male and female kittens and adult cats were given p-chlorophenylalanine orally.2. After treatment, some of the male cats showed mounting behaviour and the kittens and non-oestrous females showed an increase in treading and rubbing which was similar to one aspect of pro-oestrus behaviour.3. The treated animals also appeared to suffer from skin irritation and showed increased restlessness which accompanied sleep deprivation.4. Injection of 5-hydroxytryptophan stopped abnormal sexual activity and restored normal sleep for about 5 hours.5. It is concluded that 5-hydroxytryptamine-containing neurones inhibit sexual behaviour in cats and that this role can be seen in male and, to some extent, also in female animals.

5-Hydroxytryptophan