Exploratory behavior and the dual activity of some psychoactive drugs. Part 5. Alcohol.

Alcohol is reported to impair acquisition and learning processes and it is considered a depressant of the brain activities impairing rapidity and consistency of some behaviors. The experiments reported here are concerned with the exploratory performances of the already described subpopulations of Albino mice under the effect of alcohols of different types.

Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats.

Learning/memory deficits in senescent animals are widely used as a tool to evaluate the therapeutic potential of agents for treatment of age-associated cognitive dysfunction. As assessed in the Morris water maze test, aged (21-24 months) rats showed a variable loss of spatial memory. Aged non-impaired rats performed as well as young subjects, while aged impaired rats exhibited a severe and persistent place-navigation deficit. Passive avoidance retention was similarly affected in the two aged subpopulations. Chronic oral administration of phosphatidylserine (50 mg/kg/day for up to 12 weeks), a pharmacologically active phospholipid, was found to improve both the spatial memory and the passive avoidance retention of aged impaired rats. Results are discussed with reference to the phosphatidylserine-induced improvement of age-associated deterioration of brain functions in rats.

Exploratory behavior and the dual activity of some psychoactive drugs. Part IV. Neuroleptics.

Exploration is an essential, life-preserving component of animal higher nervous functions. The experiments presented here show that exploratory behavior may differ in relation to the subject's emotional baseline, and that accordingly, it is affected differently by various neuroleptics.

Difference in learning and retention by Albino-Swiss mice. Part 5. Effect of some antidepressants.

According to the methods described earlier (1), the effect of some antidepressants on memory retention in "good" and "poor" learning mice was studied. The present study indicates that several antidepressants have different activity on memory retrieval of the two subtypes of animals, which is directly responsible for the results here reported. In general terms, the data obtained show that, in addition to the classical antidepressant activity, some derivatives may exert a behavioral disinhibition.

Exploratory behavior and the dual activity of some psychoactive drugs. Part III. Antidepressants.

Exploration is an essential, life-preserving component of animal higher nervous functions. The experiments presented here show that exploratory behavior may differ in relation to the subject's emotional baseline, and that accordingly it is affected differently by various antidepressants.

Effect of some anesthetics on memory and exploration.

A light ether anesthesia in laboratory mice resulted in the complete drop of their memory retrieval to zero for more than three days after the administration. On the contrary, mice that underwent the exploration test after the light ether anesthesia performed as expected, confirming that impairment of memory does not necessarily reflect on exploratory performance. The effect of some anesthetic drugs was then studied on memory retrieval and exploratory behavior. Within this general framework, the anesthetics here studied all worsen memory retrieval, however without inducing clear and long-lasting amnesic effect comparable to that exerted by ether anesthesia. Contrarily, the classically amnesic drug scopolamine, orally administered, enhances memory retrieval and improves exploration.

Exploratory behavior and the dual activity of some psychoactive drugs: Part II.

Exploration is an essential, life-preserving component of animal higher nervous functions. The experiments presented here show that exploratory behavior may differ according to the experimental subject's emotional baseline, and that exploratory performance is accordingly affected differently by some nutrients and central stimulants.

Activity of phosphatidylserine on memory retrieval and on exploration in mice.

Recent human and animal studies have reported about neurochemical and behavioral changes occurring during aging. Bovine brain phosphatidylserine (BC-PS) administered in vivo was reported to produce changes in the metabolic status of the brain and in behavioral performances. Within the Albino-Swiss strain of mice two subtypes have been shown to exist with different learning and memory retention abilities. These animals also have different reactions to various psychoactive drugs. The experiments presented here deal with the hypothesis that BC-PS may show different effects according to the starting emotional status of the animals. The technique of intracerebral injection was employed to ensure active concentrations of BC-PS in the brain. The results reported here show that BC-PS clearly improves performances in the subtype of mice with poor exploratory activity.

Exploratory behavior and the dual activity of some psychoactive drugs. Part 1.

Animal behavior in a free environment involves the orienting reflex, a major component of which is exploratory behavior. Exploration is an essential, life-preserving component of animal higher nervous functions and the experiments presented here show that exploratory behavior may differ according to the experimental subjects' emotional baseline. Exploratory performance may accordingly be affected differently by psychoactive drugs.

Norepinephrine-mediated suppression of apomorphine-induced aggression and locomotor activity in the rat amygdala.

The effect of injections of norepinephrine (NE)-depleting toxin DSP-4 into the central amygdala (AMY) on apomorphine-induced fighting (AIF) was studied. In addition, the influence of such treatment on related parameters such as spontaneous activity, pain sensitivity and changes in locomotion after (+)3-PPP or apomorphine (1 mg/kg SC each) were verified. Finally, injections of NE or phenylephrine into the AMY five min before AIF were performed. DSP-4 induced marked (-71%) and selective fall in NE within the AMY accompanied by significant increase in aggressive response to 5 mg/kg of apomorphine. DSP-4-treated animals were less active in the open field and more sensitive to pain in a hot plate test. They were also more responsive to locomotor-augmenting action of apomorphine. Significant suppression of AIF was seen after injections of NE and phenylephrine into the AMY. The results suggest that NE input to the AMY plays an inhibitory role in dopamine-related locomotion and aggressivity. Moreover, amygdalar NE appears to be involved in general activity and pain perception modulation.

Difference in learning and retention by Albino-Swiss mice. Part IV. Effect of some nutrients.

According to the preceding papers, the possible difference in activity of some nutrients on memory retrieval of "good" and "poor" learning mice was studied. Among the substances used, only phenylalanine significantly improved memory recall of poor learning mice. On the contrary, tryptophan, tyrosine, phosphatidylserine and choline did not influence memory retention of previously learned avoidance of both poor and good learning mice.

Enhanced apomorphine-induced fighting in rats after prolonged oral treatment with drugs altering noradrenergic transmission.

Male Wistar rats were given orally for seven days water, clonidine (0.125 or 0.25 mg/kg bid) or S3341, a new clonidine-like drug (2.5 or 5.0 mg/kg bid) and afterwards pairs of rats were injected ip with 2.5 mg/kg of apomorphine (APO). Water-treated animals did not behave aggressively. Clonidine and S3341 both induced clear aggression when combined with a subthreshold dose of APO. Some degree of hyperirritability developed in these two groups during drug treatment when observed in the home-cage. No significant changes in aggressive behavior were noted upon acute administration of both drugs, though some tendency to augment aggressivity could be observed after clonidine (0.25 mg/kg po). It is suggested that noradrenergic neurons play an inhibitory role in APO-induced fighting.

Effect of chronic administration of alprazolam and adinazolam on clonidine- or apomorphine-induced aggression in laboratory rodents.

The activity of chronic (3 weeks) treatment with the triazolobenzodiazepines, alprazolam and adinazolam, on clonidine- and apomorphine-induced aggression were studied. Adinazolam, like desipramine, potentiated aggression induced by clonidine while diazepam and alprazolam completely abolished it. In the apomorphine-induced aggression, adinazolam suppressed both aggressivity and stereotypy, while diazepam slightly potentiated it. Alprazolam did not modify the effect of aggression induced by apomorphine. On the whole, while adinazolam seemed to develop an activity closer to that of a classical antidepressant like desipramine, alprazolam appeared to be more similar to the benzodiazepines on clonidine-induced aggression in mice. Compared to desipramine and diazepam, adinazolam left these two effects induced by apomorphine almost unchanged. The experiments performed showed differences between the profiles of action of the two triazolobenzodiazepines studied.

Difference in learning and retention by Albino Swiss mice. Part III. Effect of some brain stimulants.

According to the two preceding papers, the possible difference in activity of brain stimulants on memory retrieval of "good" and "poor" learning mice was studied. Among the drugs studied, caffeine, oxiracetam and nicotine significantly improved memory recall of poor learning mice. On the contrary, methylphenidate, fipexide and piracetam did not significantly modify memory retention of previously learned avoidance of both poor and good learning mice.

Age-dependent spontaneous EEG bursts in rats: effects of brain phosphatidylserine.

During aging, male Sprague-Dawley rats display increasing frequency of bursts of seizure-like EEG patterns. They also have a decreased retention of passive avoidance response and a loss of spontaneous alternation in a Y maze. A study was made on the effects of chronic administration of phosphatidylserine in aged rats. It was found that BC-PS reduced by 65% the number of seizures, and by 70% their duration. It also facilitated retention of passive avoidance and of spontaneous alteration behavior. These results suggest that phosphatidylserine can affect electrophysiological and behavioral parameters in aged rats probably by counteracting age-related biochemical changes.

Effect of 6-OHDA injected into the locus coeruleus on apomorphine-induced aggression.

Bilateral microinjections of 6-hydroxydopamine (6-OHDA) into the nuclei loci coerulei (LC) of male Wistar rats resulted in significant depletion of mesencephalic and striatal norepinephrine, accompanied by a small reduction in dopamine content only in the striatum. Apomorphine (2.5 mg/kg IP) induced marked aggression consisting of prolonged posturing, vocalization and attacks only in 6-OHDA lesioned animals. Biochemical analysis revealed that 6-OHDA antagonized the ability of apomorphine to raise the serotonin concentration in the striatum. It is concluded that the LC neurons play an inhibitory role in apomorphine-induced aggressiveness and the involvement of serotonergic neurons is suggested.

Chemical lesions of the nucleus accumbens septi in rats: effects on muricide and apomorphine-induced aggression.

To assess the influence of monoaminergic neurones in the nucleus accumbens septi (NAS) on muricidal and apomorphine-induced aggression, bilateral intraaccumbens injections of relevant neurotoxins were performed. Neurochemical effects in the mesolimbic area (NAS and tuberculi olfactorii) and striatal tissue were investigated using high performance liquid chromatography. 6-Hydroxydopamine (6-OHDA) with desipramine pretreatment significantly decreased mesolimbic dopamine (DA) metabolism, 5,7-dihydroxytryptamine (5,7-DHT) plus desipramine diminished serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), while DSP-4 depleted noradrenaline (NA), 5-HT, 5-HIAA and tryptophan in the mesolimbic area. No significant biochemical changes were observed in the striatum. Behaviourally, 6-OHDA-treated rats were markedly more aggressive in the apomorphine-induced fighting test. Similarly, DSP-4 injections into the NAS (10 micrograms/1 microliter) enhanced this type of aggression. The 5,7-DHT lesion did not alter apomorphine-induced fighting. None of the neurotoxins induced muricidal behaviour. It is concluded that dopaminergic postsynaptic receptors in the NAS may be involved in the pro-aggressive effect of apomorphine. The results support the hypothesis that NA-containing neurones play an inhibitory role in apomorphine-induced aggression and suggest that such a DA-NA interaction might occur in the NAS.

Reversal of scopolamine-induced amnesia by phosphatidylserine in rats.

Scopolamine (2 mg/kg IP) and propranolol (55 mg/kg IP), given before a single learning trial, reduce retention of a passive avoidance response in rats. Phosphatidylserine, 30-60 mg/kg IP, antagonizes the amnesic effect of scopolamine but not that of propranolol. The retention of the passive avoidance response is not affected by phosphatidylserine given alone. The results indicate that this phospholipid selectively counteracts the action of scopolamine on passive avoidance acquisition, probably via a cholinergic mechanism.

Difference in learning and retention by Albino-Swiss mice. Part 2. Effect of some anxiolytic drugs.

According to the method described earlier (1), the effect of some anxiolytics on memory retention in "good" and "poor" learning mice was studied. While the classical benzodiazepine (diazepam) significantly improves performance of both sub-populations of mice, non-benzodiazepine anxiolytics worsen that of poor learners and triazolobenzodiazepines increase performance.