An experimental model of behavioral hyperactivity and its modification by various drugs: Implications for minimal brain dysfunction / Perspectives in differentiation and hypertrophy

The neuropharmacological model used in this study has indicated that hyperactivity in rats results from cholinergic overactivity due to increased brain acetysholine level. Support for this contention comes from the fact that the hyperactivity induced in rats is significantly (P<0.001) attenuated by a cholinergic antagonist-atropine sulphate. Whatever the complexities of the receptor mechanisms, this observation has clear implications both for our understanding of the etiology of hyperkinesia and its treatment. In addition, the fact that chemical methods of treatment clearly ameliorate the syndrome has supported the belief that hyperkinesia is primarily a biologic rather than a psychological disorder. However, experimental animals are not humans and it is therefore quite possible that drugs have effects in man which are different from those in rats. Thus, obvious caution must be used in applying these results and those of other experiments to the understanding of hyperkinesia. Nevertheless, the results presented in this study suggest that anticholinergics might be useful chemotherapy for hyperkinesia (AU)

Current concepts of abnormal motor disorder: an experimental model of attentional deficit disorder

An attempt was made to indicate the neuropharmalogical relationship between Parkinson's disease, Huntington's chorea, tardive dyskinesia and Attentional Deficit Disorder. In the case of the latter, an experimental model has been prersented indicating cholinergic dysfunction in the nigro-striatal pathway. Postulates are proposed which will enable us to understand the many factors responsible for these clinical states. (AU)

Effects of reserpine, tranylcypromine, haloperidol and Fla-63 on physostigmine - Induced hyperactivity in rats

The effects of bis (4-methyl-l-homopiperazinyltio - carbonyl) disulphide (FLA-63), haloperidol, reserpine and tranylcypromine on physostigmine-inducedhyperactivity in rats were studied using jiggle platforms to measure motor activity levels. Haloperidol (0.025 mg/kg). On the other hand FLA-63 (2.5 mg/kg) and tranylcypromine (20 mg/kg) attenuated the effect of physostigmine during the first thirty minutes of testing and caused a potentiation during the next thirty minutes. All drugs were administered intraperitoneally. These results support the hypothesis of an interaction between the cholinergic and catecholminergic systems in the central nervous system (AU)

A preliminary study of the sedative effects of annona muricata (sour sop)

Alcholic extract from the ripe fruit of Annona muricata decreases the motor activity and prolongs the barbiturate (thiopentone sodium) sleeping time of rats. The latter effect is thought to be due to a central action of the extract. The findings reported here support the local claim by some that Annona muricata (sour sop) has sedative properties (AU)

An investigation of experimentally induced behavioural hyperactivity: a neuropharmacological study

The cardinal features of the hyperkinetic child syndrome is excessive non-goal directed motor overactivity and impulsivity. Although hyperactive children constitute a small part of their age group, 4 percent - Steward et al 1966, their effects on peers and demands on teachers and parents are far out of proportion to their number. In addition, the linkage between hyperkinesia and adult psychopathology (like-emotional immaturity, inability to attain goals, feelings of hopelessness and poor self image) has been inferred from longitudinal, retrospective and family studies (Arnold et al 1972, Huessy 1974, Robins 1966). The present drugs of choice for the treatment of hyperkinesia (central nervous system stimulants like methylphenidate and d-amphetamine), have serious side effects and long periods of administration are known to cause psychosis (Laufer and Denhoff 1957). In the light of the above problems, fundamental research aimed at elucidating the biochemical determinants of hyperkinesia would be very useful, as this might result in better pharmaco-therapy for the syndrome. However, caution should be excercised in extrapolating results from animal to man. Since a functional interrelationship exists between dopaminergic and cholinergic systems (Sethy and Van Woert 1974), in the extrapyramidal system (this is important for the control of motor activity in man and other mammals), it was therefore hypothesized that motor hyperactivity could be due to a cholinergic inbalance in the brain. Rats' motor activity would seem a reasonable model for this study, as the main symptom of this syndrome is motor hyperactivity. Female rats (mean body weight 200 ñ 5G) were used for this study. Motor activity was measured with jiggle platforms which monitor the gross motor activity of the test animals as opposed to photoelectric activity cages which only measure animals locomotion. All drugs used for this study were injected intraperitoneally at a volume of 0.1ml, and the testing period for each rat was 60-min. Physostigmine at dose levels (0.01 - 0.18mg/kg) significantly increased rats motor activity as compared to saline controls. This increase in motor activity was also obtained when physostigmine at 0.05mg/kg was injected daily for four days. Atropine sulphate (5 and 10 mg/kg) attentuated the physostigmine induced increase in motor activity. However, the physostigmine induced excitation was potentiated by d-amphetamine at 1, 2 and 4mg/kg. These effects occurred whether physostigmine was injected before or after atropine and d-amphetamine. The effect of physostigmine on motor activity is central as neostigmine did not induce any stimulation of rats' motor activity. In addition reserpine, phenobarbitone, haloperidol and practocol (a beta-adrenergic blocking drug), attentuated the physostigmine-induced increase in motor activity, while phentolamine and tranylcypromine (MAO Inhibitor) did not affect the physostigmine-induced excitation. These results are discussed in conjunction with the findings of other workers and is concluded that: (i) increasing the acetylcholine level of the rats brain with an anticholinesterase (physostigmine) induces motor hyperactivity: (ii) anticholinergics and neuroleptics are capable of attenuating this physostigmine-induced motor hyperactivity. (iii) the fact that d-amphetamine potentiated the physostigmine-induced motor hyperactivity may exlain the observation that following d-amphetamine or methylphenidate treatment, some hyperkinetic children (30 percent) manifest a worsening of their symptoms. (Satterfield et al 1972). If in some subtypes of hyperkinetics, a cholinergic dysfunction is present, then it follows on the basis of the present study that d-amphetamine will excercebate their condition, while anticholinergics might be useful therapy (AU)

Differential attenuation by atropine and d-amphetamine on hyperactivity: possible clinical implications

Intraperitoneal administration of physostigmine (0.025 to 0.18 mg/kg) to rats resulted in dignificant increases in motor activity as measured with jiggle platforms. Doses of physostigmine 0.2 mg/kg or more decreased motor activity. The physostigmine-induced hyperactivity was attenuated by atropine (5 mg/kg) given before or after physostigmine (0.05 mg/kg). On the contrary, d-amphetamine (2 mg/kg), given before or after, significantly potentiated the physostigmine-induced increase in motor activity. The relevance of the cholinergic system in mediating hyperactive behaviour in children is discussed. (AU)

The possible usefulness of anti-cholinergic drugs in the treatment of the hyperkinetic syndrome in children: Part II

Rats that were treated with physostogmine (0.05 mg/kg) manifested marked hyperactive behaviour. In a previous study, dexamphetamine (0.02 mg/kg) did not antagonize the physostigmine-induced locomotor hyperactivity. This study indicates that atropine (10 mg/kg) mitigates physostigmine-induced hyperactivity of rats' locomotory behaviour. It is therefore postulated that anticholinergic drugs may have a place in the therapeutic management of the hyperkinetic syndrome observed in children (AU)