Luigi Molinengo

Effects of thioperamide on locomotor activity and on memory processes

1. Rats were tested in an open field. Thioperamide given i.p. 30 minutes before the tests produced an increase of locomotor activity at 2 mg/kg and no behavioral effect at 5 mg/kg. 2. The repetition of the open field tests caused a reduction of ambulation in three successive tests. This effect was increased by thioperamide 2 and 5 mg/kg given after the tests, suggesting that this compound improved memory consolidation.

Action of caffeine, L-PIA and their combination of memory retention in the rat

Rats were trained to run in a staircase and to stop on the 3rd, 6th, 9th and 12th steps. The increase of errors (arrest on any other step) after 2O days of interruption of the daily training was evaluated after a chronic administration (15 days) of L-PIA (N6-(L-phenylisopro-pyl)adenosine) 1 mg/kg/day; caffeine 15,45,8O mg/kg/day and of the combination of L-PIA 1 mg/kg/day with 15, 45 and 80 mg/kg/day of caffeine. In the controls and after caffeine administration, the interruption of the daily training caused a reduction of correct responses. After L-PIA alone or in combination with caffeine there was no reduction of correct responses after 2O days of no daily training. These results indicate that in the behavioral situation of our experiments there was no antagonism between caffeine and L-PIA.

Combined action of thioperamide plus scopolamine, diphenhydramine, or methysergide on memory in mice.

The aim of the present experiments was to test the role played by the interaction of the selective H3 receptor antagonist, thioperamide, with the cholinergic, histaminergic, and serotonergic systems in modifying memory. The behavioral tests used (open-field and passive-avoidance repetition) were selected on the basis of the action displayed by thioperamide in these behavioral situations. Posttrial administration of thioperamide (5 mg/kg) resulted in an improvement in memory consolidation, as tested in the repetition of the open-field test, but repeated posttrial administration of thioperamide (2 or 5 mg/kg) had no effect in the repetition of passive avoidance test. Scopolamine (2 mg/kg) caused a deterioration in the memory processes in both tests: this effect was blocked by 2 mg/kg of thioperamide, which was itself ineffective in the test. These results may suggest that both the improvement in memory due to thioperamide and its antagonism of the amnestic effects of scopolamine are determined by activation of central cholinergic systems, due to thioperamide inhibition of H3 heteroreceptors. Diphenhydramine (2 or 10 mg/kg) was itself ineffective in the tests, but counteracted the memory improvement caused by thioperamide in the repetition of the open-field test. The effect of diphenhydramine is discussed in terms of interactions between histaminergic and cholinergic systems. Methysergide counteracted the effect of thioperamide in the open-field test only at a high dosage (50 mg/kg). The possible implication of serotonergic systems on the effects of the methysergide-thioperamide interaction in the memory process is discussed.

Behavioral and Neurochemical Effects Induced by Subchronic l-Deprenyl Administration

(-)Deprenyl was administered orally to rats for 15 days. In the staircase maze, a reduction of incorrect responses was observed at 0.9 mg/kg/day; higher or lower doses (3.5 or 0.35 mg/kg/day) were ineffective. In the same range of doses, the subchronic administration of (-)deprenyl did not modify the levels of norepinephrine, 5-hydroxytryptamine, 5-hydroxyindolacetic acid or the density and affinity of alpha-noradrenergic receptors in the cortex, olfactory system, hippocampus and striatum. An increase of the dopamine and a reduction of dihydroxyphenylacetic acid levels was observed only at the highest tested doses, at which no behavioral modification was observed. Only at 1.0 mg/kg/day did (-)deprenyl increase the acetylcholine (ACh) levels in the olfactory system, hippocampus and striatum. This neurochemical effect may be correlated to the behavioral effect observed in the same range of doses. We propose that this increase of ACh levels is determined by an activation of dopaminergic systems, resulting from the increase in the levels of PE caused by the inhibition of monoamine oxidase B (MAO-B) by (-)deprenyl.

Action of a chronic disulfiram administration on memory decay and on central cholinergic and adrenergic systems.

The chronic administration (15 days) of disulfiram reduced the levels of noradrenaline (NA) in the olfactory system and in the subcortex at all the tested doses (50, 200 and 400 mg/kg/day). No modification of the density (Bmax) and of the dissociation constant (Kd) for alpha 1-adrenergic receptors was observed (radioligand [3H]prazosin). Only in the hippocampus the acetylcholine (ACh) levels and the Bmax for muscarinic receptors (radioligand [3H]QNB) were increased at all doses tested. Modifications of the cholinergic system were observed in the subcortex and in the cortex only at the higher doses of disulfiram. After 20 days interruption of the daily training in the staircase maze, 50, 100 and 200 mg/kg/day of disulfiram accelerated spontaneous decay of memory. It is hypothesized that the modifications of the hippocampal cholinergic system (increase of the ACh levels and of the density of the muscarinic receptors) may be the condition determining the acceleration of the decay of memory caused by disulfiram.

Action of a chronic arecoline administration on mouse motility and on acetylcholine concentrations in the CNS.

Abstract— The modifications of mouse motility and of the levels of acetylcholine (ACh) in two sections of the CNS caused by a chronic administration of 4.5; 9.5; 28.5 and 60 mg kg‐−1 day−1 of arecoline for 20 days have been studied. At low doses (4.5 and 9.5 mg kg−1 day−1), arecoline caused no modification of the ACh levels and of the motility. The higher doses (28.5 and 60 mg kg−1 day−1) caused a reduction of the mouse motility and an increase of the ACh levels in the subcortical structures of the CNS of the mouse.

Action of thyroid hormones, diazepam, caffeine and amitriptyline on memory decay (“forgetting”)

Abstract A straircase maze has been used to test the modifications induced by a chronic administration of caffeine, amitriptyline, diazepam and hypo or hyperthyroidism in the decay of the rat performance (“forgetting”) caused by the interruption of the daily training. Diazepam 0.35 mg/kg and 0.07 mg/kg, caffeine 21 mg/kg, amitriptyline 1 mg/kg, increased the forgetting. Hyperthyroidism caused no modifications of behaviour; high hypothyroidism increased and low hypothyroidism completely abolished the decay of rat performance consequent to the daily training interruption.

Habituation of exploratory activity in rats: Action of N6phenylisopropyladenosine, caffeine and their combination

1. L-PIA (0.2 mg/kg), caffeine (15 mg/kg) and their combination were given subcutaneously to rats tested in open field. 2. The acute administration of L-PIA reduced ambulation. Caffeine alone was ineffective but increased ambulation in combination with L-PIA. These effects may have been determined by an interaction of L-PIA and caffeine on adenosine receptors. 3. Tolerance to L-PIA was observed after a chronic administration (20 days). The chronic administration of caffeine alone or in combination with L-PIA increased ambulation. 4. In the habituation test the reduction of ambulation in the 3 successive trials was increased by L-PIA. Caffeine did not antagonize the L-PIA effect and, in part, had the same effect. These results suggest that L-PIA and, in part, caffeine improve memory consolidation in open field, and do not support the notion that L-PIA and caffeine action on memory processes is due to an interference on adenosine receptors.

The effect of chronic atropine administration on mouse motility and on ACh levels in the central nervous system.

Changes in mouse motility and CNS cortical and subcortical ACh levels were studied after chronic (20 days) administration of 30, 40 and 60 mg/kg/day atropine. An increase in motility similar to that induced by acute atropine administration was observed, whereas the ACh levels reduction caused by acute administration was not repeated. These results suggest that changes in mouse motility caused by atropine are not correlated to its modification of ACh levels in the CNS.

Action of 5-hydroxytryptamine, histamine and methergoline on phagocytosis.

Polymorphonuclear leukocytes of guinea pig were used to study the action of 5-hydroxytryptamine, histamine and methergoline on phagocytosis. Phagocytosis was reduced by 5-HT; this effect was only in p