Mesolimbic deficits exacerbate amphetamine treatment: clinical implications for drug abusers

Amphetamine, a common drug used by abusers, is able to produce a schizophreniform psychosis in man. The experiment reported here examined amphetamine in relation to its role in the nucleus accumbens septi (NAS) and the globus pallidus. The effects produced by apomorphine, a direct dopamine (DA) agonist, were compared with those of amphetamine, a known indirect DA agonist. The data revealed that amphetamine in NAS-lesioned animals produced very active stereotypy which intensified with time. This effect was blocked by pallidal lesioning. Apomorphine in pallidectomised rats produced persistent stereotypy, but of diminished intensity. The results are discussed in terms of the mediating roles of the NAS and globus pallidus on behavioural sequelae. (AU)

The effect of atropine and physostigmine sulphates on behavioural arousal in the developing rat

The purpose of this study was to observe the effect of atropine and physostigmine sulphates on the behavioural arousal of the developing rat with the aim of determining the exact age at which these drugs became effective. The spontaneous motor activity of the rats aged 15 - 28 days was measured using photocell activity cage, motor activity was measured for sixty minutes while the observation period in the Y maze was 3 minutes, subsequent to the administration of atropine, physostigmine or saline. The drugs were administered intraperitoneally. Control studies revealed that the 15 - 18 day old rats habituate slowly while the 20 - 28 day olds show a more precipitous decline in motor activity as time progressed. This age-related ability to habituate resulted over a period of 60 minutes, in higher activity scores in younger rats. This decrease in motor activity has been attributed to a gradually developed acetyl-choline inhibitory system. In contrast, in the Y maze, there were increases in the activity scores as the rats aged. It has been suggested that the age-related increase in activity is a result of an increased ability to explore. The intraperitoneal administration of atropine resulted in decreases in the spontaneous motor activity of the 15 - 18 day olds. At 19 days however, atropine had no effect on the activity recorded. These increases continued until day 25, after which atropine had virtually no effect on activity. The decrease in the motor activity of the drug-treated 15 - 18 day olds may be a result of drug blockade of cholinoreactive elements of the reticular activating system. In addition, the increase in activity observed between 21 - 25 day olds may be related to (i) an alteration in the cholinergic/dopaminergic balance of the brain in favour of the dopaminergic system (ii) the development of a cholinergic inhibitory system after day 20 of life. Compared with saline controls, the administration of physostigmine (0.2 mg/kg) to rats aged 15 - 21, 25 and 28 days resulted in significant decreases in the activity of the 15 - 20 day olds only. Increases in the locomotor activity of the 21, 25 and 28 day old rats were observed. Physostigmine (0.05 mg/kg) was administered to 16, 18, 21, 25 and 28 day old rats. At this dosage, a depressant effect was noted in the 16 day olds only. By day 18, however, a tendency towards an increase in motor activity developed. By 21 days, a definitely significant increase in motor activity was detected. The decrease in the activity of the younger rats (15 - 20 days) is possibly due to a combination of drug action at the neuromuscular junction and on response inhibition. Increases observed after day 20 are a result of physostigmine-induced increase in bothcortical and behavioral arousal in the intact animal. The changing pattern of the rat's response to the effects of atropine and physostigmine may be correlated with the gradual maturation of forebrain inhibitory structures (frontal neocortex and hippocampus) responsible for the modulation of reticular excitability (AU)

Relationship between separation-age of offspring and level of arousal as an indication of behavioural disturbance

Forty Sprague-Dawley rats were separated from their mothers at 2, 3, and 4 weeks respectively and were either reared in groups or in isolation for four weeks. Spontaneous motor activity was determined in activity cages. Results showed that rats separated at 4 weeks and reared in isolation showed the highest level of motor activity. This would imply that the longer the pup spent with the mother prior to separation the greater the impact of the separation experience (AU)