Search

The concentration of dopamine (DA) and norepinephrine (NE) are decreased to a maximum of 40% and 20%, respectively, in the substantia nigra of precollicular and prenigral decerebrated cats previously treated with benzoctamine (Tacitin) (0.7 mg/kg i.v.), while the tyrosine-hydroxylase and MAO activities remain unchanged. Muscle stretch reflexes recorded simultaneously showed a significant decrease of stretch tension which is evoked by a clear reduction of Ia discharges of the primary muscle spindle afferents. It would appear that benzoctamine suppresses reflexly evoked gamma-motoneurone discharges.

Intraperitioneal injection of d-amphetamine sulfate, 0.3-3 mg/kg, led to a marked rise in dopa formation in the dopamine rich areas c. striatum and mesolibbic cortex of the rat brain inhibiton of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCL (NSD 1015). However, amphetamine given in a dose of 10 mg/kg decreased the tyrosine hydroxylation rate in the mesolimbic cortex as well as the norepinephrine containing neocortex. In combination with haloperidol the stimulating effect of the neuroleptic on dopa formation was markedly potentiated by amphetamine in rat forebrain. Also, amphetamine potentiated the haloperidol induced increase in dopamine release in vivo measured as 3-methoxytyramine formation. The functional antagonists haloperidol and d-amphetamine appear to have synergistic effects on dopaminergic neurons.

The neostriatum of adult rats was investigated by means of the Golgi rapid impregnation procedure following surgical (unilateral stereotaxic MFB lesions or complete deafferentation) and pharmacological (i.p. application of pargyline, amphetamine, reserpine, haloperidol in submaximal doses) pretreatments, respectively. The neurons of this brain area--as a whole, ten types can be differentiated according to morphological criteria--do exhibit a characteristic impregnation behavior being in proportion to the mode of pretreatment in each case. The impregnation behavior of the neurons is postulated to depend on the polarization state of their membranes which may be explained in pharmacological and physiological terms.

The effect of (+)- and (-)-tranylcypromine (TCP), (-)-deprenyl and pargyline was tested and the interaction of these MAO inhibitors with tyramine and noradrenaline was compared on the circulation of the cat and on the isolated guinea-pig atria. 1. Anesthetised cats: An i.v. injection of 1 mg/kg of (+)- as well as (-)-TCP leads to an increase in the blood pressure and dp/dtmax. This effect is getting weaker on repeated doses. (-)-Deprenyl and pargyline decrease blood pressure and dp/dtmax. After a preadministration of (+)-TCP or pargyline the effect of tyramine on the blood pressure and contractility is prolonged. (-)-TCP prolongs slightly the cardiac effect of tyramine and is less effective than (+)-TCP. (-)-Deprenyl does not influence the effect of tyramine. The noradrenaline effect is not affected by the MAO-inhibitors. 2. Conscious cats: An i.v. injection of (+)- as well as (-)-TCP increases the blood pressure and decreases the heart rate. Desipramine (DMI) blocks this effect. Preadministration of (+)- as well as (-)-TCP and pargyline, but not (-)-deprenyl, potentiates the effect of tyramine on the blood pressure. According to this activity one can arrange these MAO-inhibitors as follows: (+)-TCP greater than (-)-TCP greater than pargyline. 3. Atrial preparations of guinea pigs: (+)- and (-)-TCP have a positive inotropic effect at concentrations from 10(-6) to 10(-5) mol/l, which is blocked by bupranolol and DMI. A pretreatment with reserpine prevents the effect of (-)- and weakens that of (+)-TCP. (+)-TCP, pargyline and (-)-deprenyl potentiate the effect of tyramine, while that of noradrenaline is potentiated by (+)- as well as (-)-TCP and (-)-deprenyl.

The nucleus raphes dorsalis of the adult rat was investigated by means of fluorescence histochemical and neurohistological methods. After application of Falck-Hillarp-technique characteristics 5-HT-fluorescence could be seen in many, albeit not all of the cells of this nucleus. After using the rapid Golgi impregnation technique, 3 neuron types could be demonstrated: type-1-neurons (polygonal neurons with somatic spines); type-2-neurons (fusiform neurons), and type-3-neurons (pyriform neurons). The type-1- and type-2-neurons are, due to their different axon projection mode, considered to be efferent raphe neurons. The type-3-neurons are thought to be raphe interneurons. The type-1-neurons are inferred to represent the 5-HT producing neurons of the nucleus raphe dorsalis.

The inhibition of monoamine oxidase (MAO) A and B by amitriptyline, pargyline and pirlindole was measured in heart and brain homogenates of rats with tryptamine and beta-phenylethylamine as substrates. The tricyclic antidepressant amitriptyline inhibited MAO B stronger in the brain (Ki = 8.41 X 10(-6) mol/l) as well as in the heart (Ki = 7.03 X 10(-5) mol/l) compared to the A-form (1.51 X 10(-4) and 1.03 X 10(-4) mol/l, respectively). Pargyline diminished the activity of both enzyme forms of the heart in the same range (4.29 and 1.60 X 10(-6) mol/l), whereas in the brain the B-form was blocked in a more pronounced manner, too (5.80 X 10(-8) and 4.01 X 10(-6) mol/l, respectively). In contrast to amitriptyline and pargyline pirlindole inhibited the MAO with tryptamine as a substrate in the brain 100 times (2.49 X 10(-7) mol/l) and in the heart nearly 1000 times (3.42 X 10(-8) mol/l) more than with phenylethylamine as a substrate (5.21 and 5.99 X 10(-5) mol/l, respectively). These results show that amitriptyline and pargyline are relatively selective inhibitors of MAO B, whereas pirlindole blocks the A-form of MAO much stronger than MAO B.

The neostriatum of adult rats pretreated wit pargyline was investigated by means of the rapid Golgi procedure. An hitherto unknown spine-bearing neuron typ with a soma size ranging from 6 to 8 microm could be demonstrated. Owing to its morphological features, this neuron type is regarded to be a striatal interneuron. The mode of transmission and the functional role of these neurons within the caudatus-putamen-complex is still to be examined.

Changes in neurotransmitter concentrations, which are brought about by the administration of neurotropic pharmaceuticals to albino rats at the time of differentiation of the brain, may have a lasting effect upon the reactivity and adaptability of adult animals to environmental factors and give rise to specific patterns of behavior. 1. Pargyline, when administered neonatally, resulted in a reduction of learning power, decrease in the power of retention, as well as reduction of the decision-making ability. 2. Reserpine gave an improvement of learning power, but simultaneously decreased both the power of retaining what had been learnt and the decision-making ability. 3. Pyridostigmine gave a marked improvement of adaptability which was evidenced in higher learning power, greater retentiveness, and better decision-making ability.