Magali Gonzalez

Rotational behavior in the cat induced by electrical stimulation of the pulvinar-lateralis posterior nucleus complex: role of the cholinergic system.

We studied the involvement of the cholinergic system in the contralateral head-eye-body turning induced in the cat through stimulation of the pulvinar-lateralis posterior nucleus complex (P-LP). In 17 cats through a cannula aimed at the P-LP, agonists and antagonists of the cholinergic system were injected. The electrical activity of the P-LP could be recorded through the same cannula or through electrodes attached to it. In addition, electrodes were implanted ipsilaterally in the dorsal hippocampus, caudate nucleus, amygdala, and superior colliculus to record through them and through one screw placed on the skull the electrical activity of those structures and of the cortical P-LP projection. Seven days after surgery, carbachol, an agonist of the cholinergic system was injected in the P-LP, and the behavior and electrical activity of the unrestrained cat (previously accustomed to a plastic cage) were recorded. A control volume of 0.9% NaCl was always injected previously. The usual drug volume injected was 1 microliter; occasionally, 2 microliter were injected. Weekly or biweekly sessions were conducted to determine (a) the threshold for cholinergic activation, (b) the threshold for turning behavior, (c) the blocking effect of local atropine sulfate injected previously, (d) the effect of haloperidol previously injected (locally or systemically), and (e) the effect of dioxolane, an exclusive muscarinic agonist. In 14 of 17 cats, contralateral turning behavior was evoked by carbachol. In two of the three cats that did not respond to carbachol, dioxolane induced turning. The effect of dioxolane was similar to that of carbachol when tried in five cats. Besides turning behavior, carbachol produced numerous symptoms due to cholinergic activation. Atropine blocked the rotational effect of carbachol in all cats, and haloperidol blocked it in 68% of them. Electrolytic coagulation of the dorsal hippocampus surrounding the P-LP did not disturb the effects induced by carbachol. These experiments show that both systems of the P-LP, cholinergic and catecholaminergic, are involved in the contralateral turning. We conclude that the effect induced by carbachol is due to activation of muscarinic receptors because it is totally blocked by local atropine sulfate and is reproduced by dioxolane, an exclusive muscarinic agonist.

Effects of p-chloro-phenylalanine on the behaviors induced by apomorphine and amphetamine in adult cats

1. The effects of serotonin depletion on the behaviors evoked by apomorphine or amphetamine are analyzed. Amphetamine (5 mg/kg, s.c.) or apomorphine (2 mg/kg, s.c.) were administered to fourteen adult mongrel cats. Inhibition of tryptophan hydroxylase was achieved by intraperitoneal injection of p-chlorophenylalanine (100 mg/kg daily for three consecutive days). Serotonin depleted animals were tested with either apomorphine or amphetamine (same doses as above). 2. Behaviors evoked by both drugs were recorded and quantified. The following behaviors were rated: motility (locomotion), alertness, fear, indifference, olfaction and lateral head movements. 3. Biochemical analysis of the raphe dorsalis and caudate nuclei of p-CPA treated animals showed an average drop in serotonin concentration of 77%. Serotonin depletion induced statistically significant changes in the following behaviors in amphetamine-treated cats: locomotion, fear, lateral head movements and alertness. Serotonin depleted cats tested with apomorphine showed significant changes only in olfaction and indifference behaviors. 4. Serotonin appears to play a significant modulatory role in some of the behaviors evoked by amphetamine, specially locomotion. Such role is less evident for the behaviors evoked by apomorphine.

Effects of SCH 23390 and sulpiride on the behaviors evoked by amphetamine and apomorphine in adult cats

1. The aim of the present study was to analyze whether the dopaminergic D1 and D2 receptors are involved in the production of the behaviors evoked by parenteral administration of amphetamine and apomorphine in adult cats. 2. Fifteen mongrel cats of both sexes were injected, in separate sessions, with 2.5 mg/kg of amphetamine and 2.0 mg/kg of apomorphine. The D1 receptor blocker, SCH 23390 was administered (0.3 mg/kg i.p.) and after 60 min, amphetamine and apomorphine were again injected on different days. The same procedure was carried on with sulpiride in two doses (20 and 30 mg/kg i.p.). The behaviors induced by the two dopaminergic drugs, before and after the receptor blocker administration were respectively compared. The Wilcoxon signed rank test was employed for statistical analysis. Three independent observers recorded the behaviors. 3. SCH 23390 and sulpiride produced per se hypomotility and sedation, effects that were considered when analysing the results. Some of the behaviors produced by amphetamine (pupillary dilation, head movements) were slightly modified by both receptor blockers. SCH 23390 only modified the licking behavior produced by apomorphine. In contrast, sulpiride blocked almost all the behaviors elicited by apomorphine, especially when the 30 mg/kg dose was administered. It is concluded that the behaviors produced by the 2 mg/kg dose of apomorphine are evoked by its binding to the post-synaptic dopaminergic D2 receptors and blocked by sulpiride.

Cholinergic blockade with scopolamine in adult cats. Effects on the behaviors evoked by apomorphine and amphetamine

1. The aim of this work is to analyse the role that the cholinergic system could play in the production of the behaviors evoked by apomorphine and amphetamine in adult cats. These two drugs were injected s.c. in separate sessions, before and after a s.c. administration of scopolamine which blocked the muscarinic receptors. The pre and post-scopolamine results of the behaviors produced by the two catecholaminergic drugs were compared using the non-parametric Wilcoxon signed rank test. 2. In a previous step a dose-response study of the behavioral effects of scopolamine, in doses of 0.05, 0.1, 0.4 and 0.8 mg/kg was carried out in ten cats. The Kruskal-Wallis and the non-parametric multiple comparison tests were employed. A dose-dependent decrease in motility (locomotion) and a dose-dependent increase in inappetence and pupillary dilation were found. 3. In thirteen cats which were injected with 2 mg/kg of apomorphine and 2.5 mg/kg of amphetamine the findings were: 1--apomorphine after scopolamine produced a decrease in the hypermotility, compared with the results observed with the former drug previous to scopolamine; 2--with amphetamine an increase in immobility and a decrease in indifference were observed. 4. The authors conclude that the decrease in motility recorded with apomorphine and amphetamine after scopolamine, could be attributed to the proper effect of scopolamine. No explanation could be found for the decrease in indifference found by injecting amphetamine after scopolamine. 5. Considering the antagonistic effect between the dopaminergic and the cholinergic systems and that the latter one has an arousal effect, we postulate that the behavioral indifference produced by apomorphine and amphetamine could be the result of a kind of blockade of the cholinergic system when the catecholaminergic system is activated through the administration of the two cited drugs.

Effects of disulfiram, phenoxybenzamine and propranolol on the behaviors evoked by apomorphine and amphetamine in adult cats

The aim of this work was to study the role that the noradrenergic system could play in the mechanism of production of the behaviors evoked by parenteral injection of apomorphine and amphetamine in adult cats. Ten cats were injected s.c. with 2 mg/kg of apomorphine and 2.5 mg/kg of amphetamine in separate sessions. The behaviors were recorded, until control conditions were again attained. In a second stage, disulfiram was administered ip., followed by apomorphine and amphetamine in the same doses as cited above. The effects on behaviors produced by disulfiram and those of apomorphine and amphetamine were recorded by three independent observers. Comparisons of the pre- and post-disulfiram behavioral results were analyzed with the help of the non-parametric Wilcoxon signed rank test. In another group of ten cats a similar procedure was carried on employing the alpha and beta noradrenergic blocking agents, phenoxybenzamine and propranolol. The noradrenergic blocking drugs, especially disulfiram and phenoxybenzamine produced by themselves a decrease in motility, in alertness and an increase in indifference and inappetence. Apomorphine and amphetamine administered after the blocking drugs showed slight behavioural modifications, reflection most of them the changes produced by the three blocking drugs. It is concluded that probably the nor-adrenergic system could be involved in the hypomotility elicited by amphetamine. NA is not involved in the induction of the other behaviors evoked by apomorphine and amphetamine.

Study of the morphological, electrophysiological and behavioral effects of unilateral kainic acid injection into the cat's substantia nigra.

Morphological, electrophysiological and behavioral studies were carried out in cats after unilateral kainic acid injection in the substantia nigra. A forced contralateral head turning and compulsive circling was observed after surgery. Fifteen days after, when asymmetry disappeared, apomorphine induced an ipsilateral head and body turning, that was blocked by haloperidol. The percentage of turning, after electrical stimulation in the superior colliculus or pulvinar-lateralis posterior complex, was affected by substantia nigra lesion. This work demonstrates that the nigro-pulvinar-lateral posterior and the nigrotectal projection modulate the capability of electrical stimulation of the target structures to elicit turning, and after unilateral substantia nigra lesion, two opposite directions of asymmetry appear, which are time-dependent and modulated by different neurotransmitters.

Study of the behavioral effects of bilateral nucleus accumbens lesions on amphetamine and apomorphine in adult cats.

The aim of the present work was to study the effects of three different types of bilateral lesions performed on the nucleus accumbens, upon the behaviors elicited in adult cats by parenteral administration of amphetamine and apomorphine, and to obtain an understanding of the functional role played by the cited structure. To this end, 10 cats received bilateral injections of 6-OHDA, 18 microg in each accumbens; 8 cats received a similar treatment with ibotenic acid (20 microg), and 11 cats were submitted to bilateral electrolytic damage. Before and after performing these lesions, in separate sessions, amphetamine (2.5 mg/kg SC) and apomorphine (2.0 mg/kg SC) were administered and their respective behaviors were compared. Besides, in a group of 10 cats, 6 of them were bilaterally injected with the above cited dose of 6-OHDA into the accumbens to determine dopamine concentration and the other four served as control. In three cats, ibotenic acid (20 microg) was unilaterally injected into the accumbens for histological analysis. The contralateral structure served as control. Finally, four cats were sham operated. The results obtained show that the accumbens in cats participates in locomotion, in stereotyped motor behaviors, and in emotional fear-like behavior. Its role in the production of motor behaviors apparently is not as important as has been reported in rodents.

Effects of naloxone on the behaviors evoked by amphetamine and apomorphine in adult cats.

1. This work was undertaken in order to study whether the opioid system is involved in the modulation of the behaviors induced by two agonists of the dopaminergic system, amphetamine and apomorphine in adult cats. 2. Naloxone, an antagonist of the mu, delta and kappa opioid receptors was administered to twelve female mongrel cats; 0.5, 1.0 and 2.0 mg/kg s.c. were injected in order to analyse its own effect of naloxone. This drug produced NREMs behavior and accordingly the cat showed an overall decrease of its activities. 3. Amphetamine (2.5 mg/kg s.c.) and apomorphine (2.0 mg/kg s.c.) were injected before and after naloxone administration (2.0 mg/kg s.c.), in separate sessions. 4. The behaviors recorded were compared. Some of the behaviors showed modifications both with amphetamine (inappetence was increased and locomotion decreased) and apomorphine (indifference and inappetence increased; locomotion and olfaction decreased). 5. These changes were considered as consequence of the NREMs behavior induced by naloxone and not as a result of a modulation by the opioid system of the activation of the dopaminergic system elicited by amphetamine and apomorphine. Regarding the mechanism of NREMs induced by naloxone probably the dopaminergic, noradrenergic and GABAergic systems may be involved.

Comparative analysis of the behaviors evoked by bromocriptine and quinpirole (LY 171555) in adult cats

The aim of this work was to compare the behavioral effects of bromocriptine and quinpirole, two agonists of the D-2 dopaminergic receptor, either injected alone or combined with the D-1 dopaminergic receptor, SKF 38393. In ten adult mongrel cats the following experimental series were carried out: i) a dose-response study with bromocriptine administering 0.5-1.0-4.0 and 8.0 mg/kg s.c.; ii) a behavioral study injecting 4.0 mg/kg of bromocriptine plus 2.0 mg/kg of SKF 38393; iii) the same analysis administering 0.5 mg/kg of LY 171555 plus 1.0 mg/kg of SKF 38393, compared with the same dose of LY 171555 plus 4.0 mg/kg of SKF 38393; iv) an analysis of the behavioral effects of 8.0 mg/kg of bromocriptine compared with 1.0 mg/kg of quinpirole. The main findings were: i) bromocriptine injected, in four different doses evoked decrease in locomotion, and increase in indifference, inappetence, pupillary dilation and limb flicks; ii) the combined administration of 4.0 mg/kg of bromocriptine plus 2.0 mg/kg of SKF 38393 did not elicit behavioral changes different to those produced by bromocriptine alone; iii) quinpirole (1.0 mg/kg) evoked more intense behaviors than bromocriptine (8.0 mg/kg); iv) comparing quinpirole injected alone with the combination of quinpirole plus SKF 38393, this latter treatment produced more intense behaviors than the former. It is concluded: i) SKF 38393 potentiates the behavioral effects produced by quinpirole; this potentiation was not found when bromocriptine was combined with SKF 38393 and ii) the more intense behavioral effect elicited by quinpirole compared with bromocriptine may be explained by the fact that the latter drug is a selective D-2 agonist, whereas the former one is an agonist of the D-2 and the D-3 receptors.