Biomedical subjects

G Di Scala

Publications and source records attributed to G Di Scala.

52 records · Page 3Linked to original sources

PubMed1990

Behavioral analysis of the effects of benzodiazepine receptor ligands in the conditioned burying paradigm.

In the conditioned burying paradigm, 10 mutually exclusive behavioral sequences were encoded in order to characterize the effects of various benzodiazepine receptor ligands. It was found that each ligand produced a specific behavioral pattern, the elements of which were consistent with results obtained in other experimental situations. Whereas anxiolytic (diazepam, Ro 16-6028) and 'anxiogenic' ligands (FG 7142) both decreased the mean duration of burying, these two classes of drugs largely differed when approaches to the prod and escape movements away from the prod were considered. The benzodiazepine receptor antagonist Ro 15-1788 was devoid of effects on all of the behavioral sequences considered. The main characteristics of these behavioral profiles persisted during an extinction test, although the animals were no longer treated. It is proposed that additional behavioral measures, or better, an ethological analysis of the behavior may increase the potency of the conditioned defensive burying paradigm.

Animals↗

PubMed1990

Aversion induced by electrical stimulation of the mesencephalic locomotor region in the intact and freely moving rat.

Electrical stimulation of the so-called "mesencephalic locomotor region" (MLR) in the acute mesencephalic and restrained rat is known to induce locomotion. In the intact and freely moving rat, electrical stimulation of an area coextensive with MLR is reported to elicit an apparently aversive type of behavioral response. Indeed, the description of this behavioral response is very similar to the description of the prototypical escape reaction elicited by electrical stimulation of the periaqueductal gray (PAG), a structure of the so-called "brain aversive system." In this study, we investigated if, as is the case for PAG stimulations, these MLR electrical stimulations are also aversive in nature. To that end, MLR-stimulated rats were subjected to the switch-off test, in which the stimulated rat learns to interrupt the stimulation by pressing a bar. It was found that electrical stimulation of MLR sites, positive for apparently aversive behavior, supports the learning of the switch-off behavior, which demonstrates the aversive nature of such stimulations. Furthermore, the switch-off latency (time elapsed between the onset of the stimulation and its offset by a press of the bar) was shown to decrease when the intensity of the electrical stimulation is increased or when the interpulse interval is decreased, which suggests that the generated aversive state is graded by the strength of the stimulation. It is, hence, proposed to extend the "brain aversive system" to the MLR.

Animals↗

PubMed1990

Differential pharmacological reactivity of aversion induced by stimulation of periaqueductal gray or mesencephalic locomotor region.

Rats were trained to switch-off aversive electrical brain stimulations applied to the periaqueductal gray (PAG) or mesencephalic locomotor region (MLR) by pressing a bar (switch-off behavior). We investigated the effects of IP injections of the benzodiazepine (BZ) receptor inverse agonist FG 7142 (2.5, 5, 10 mg/kg) or BZ receptor agonist chlordiazepoxide (CDP: 5 mg/kg) on the switch-off latency, i.e., the time elapsed between the onset of the stimulation and its offset by a press of the bar. It was found that FG 7142 decreased, whereas CDP increased the mean switch-off latency for electrical stimulation of the PAG, which is interpreted as a potentiating effect of FG 7142 and a reducing effect of CDP on the electrically induced aversive state. By contrast, neither FG 7142 nor CDP were found to affect the mean switch-off latency for MLR stimulations. These results suggest a difference in the pharmacological sensitivity to BZ receptor ligands between aversive states elicited by electrical stimulation of the PAG or MLR.

Animals↗

PubMed1990

Treadmill locomotion and aversive effects induced by electrical stimulation of the mesencephalic locomotor region in the rat.

The effects of electrical stimulation of the "mesencephalic locomotor region" and adjacent dorsolateral tegmentum were assessed and compared in the same rats in freely moving conditions or when lightly anesthetized and suspended over a moving treadmill. In freely moving conditions, electrical brain stimulation (EBS) of this part of the mesencephalon elicited mainly aversive effects (escape reactions: violent running and explosive jumps), but also ipsiversive circling and "gnawing." On the treadmill, EBS induced flexions of hindlimbs followed by locomotion (stepping) or flexions only. In addition, it was found that locomotion and flexions on the treadmill were almost exclusively elicited by EBS of sites positive for escape reactions in freely moving conditions.

Animals↗

PubMed1989

Conditioned place aversion produced by microinjections of semicarbazide into the periaqueductal gray of the rat.

Previous studies have shown that the blockade of GABA-ergic neurotransmission in the periaqueductal gray (PAG) of the rat induce flight reactions. The present study examined whether a negative affective state was produced by such a blockade. Microinjections of semicarbazide, a GABA synthesis inhibitor, into the PAG were found to produce a conditioned place aversion. In a second experiment, it was found that the potent GABA agonist muscimol antagonized the effects of semicarbazide, without producing a conditioned place preference or aversion by itself. These results suggest that the blockade of the tonic inhibition exerted by GABAergic terminals in the PAG results in both an aversive experience and an overt flight reaction.

Animals↗

PubMed1989

Conditioned place aversion produced by FG 7142 is attenuated by haloperidol.

A place conditioning paradigm was used to examine the affective properties of FG 7142, a benzodiazepine receptor inverse agonist. At the highest dose tested (10 mg/kg, IP), FG 7142 produced a significant place aversion to the drug-paired compartment. In a second experiment, haloperidol injections were given before FG 7142. It was found that haloperidol (0.2 mg/kg) significantly reduced the measured conditioned place aversion produced by FG 7142, without exhibiting any aversive or rewarding effects by itself. These results suggest that dopamine receptors are involved in the learning or expression of conditioned place aversion induced by benzodiazepine receptor inverse agonists.

Animals↗

PubMed1989

Effects of unilateral microinjections of GABAergic drugs into the inferior colliculus on auditory evoked potentials and on audiogenic seizure susceptibility.

Alteration of GABAergic neurotransmission within the inferior colliculus (IC) appears to be involved in the generation of the audiogenic seizure (AGS) susceptibility. In the present study, we provide evidence indicating that this susceptibility may result from IC neuronal hyperexcitability to sound induced by a decreased GABAergic inhibition. In a first experiment, a unilateral microinjection of bicuculline, a GABAa antagonist, into the IC of normal rats increased the amplitude of the collicular auditory evoked potential, while the microinjection of THIP, a GABAa agonist, decreased this response. In a second experiment, a unilateral microinjection of bicuculline into the IC induced AGS susceptibility in normal rats.

Acoustic Stimulation↗

PubMed1987

Evidence of Pavlovian conditioned fear following electrical stimulation of the periaqueductal grey in the rat.

Stimulation of the periaqueductal grey (PAG) has been used to support aversive conditioning in a variety of species with several experimental paradigms. However, it has not been clearly demonstrated whether the behavioral changes produced by PAG stimulation in these paradigms are mediated by associative or nonassociative mechanisms. The present studies demonstrate that electrical stimulation of the PAG in the rat may be used to support associative learning in a Pavlovian paradigm. In each experiment, a fully controlled conditional emotional response (CER) procedure was used to examine the unconditional aversive properties of PAG stimulation. In Experiment 1a, weak associative conditioning was observed when a light CS was paired with PAG stimulation over 6 conditioning trials. In Experiment 1b, robust associative conditioning was obtained with a light CS when 18 conditioning trials were used. In Experiment 2, robust associative conditioning was demonstrated with a tone CS when 6 conditioning trials were used. The results parallel those found when other aversive stimuli are used as a UCS (e.g., footshock or intraorbital air puff), and because the present experiments included the proper control procedures the results clearly indicate that the behavioral changes produced by PAG stimulation are mediated by associative Pavlovian learning mechanisms rather than nonassociative mechanisms such as sensitization or pseudoconditioning. The present technique may be useful for assessing the neuroanatomical and neurochemical substrates underlying the aversive effects of brain-stimulation, and for screening the effects of drugs on the conditional and unconditional responses produced by such stimulation.

Acoustic Stimulation↗

PubMed1986

Escape behavior produced by the blockade of glutamic acid decarboxylase (GAD) in mesencephalic central gray or medial hypothalamus.

Microinjections into the mesencephalic central gray (CG) or the medial hypothalamus (MH) of three drugs (L-allylglycine, Semicarbazide or 4,5 dihydroxy-isophtalic acid) known to block glutamic acid decarboxylase (GAD) produced a dose-dependent behavioral activation accompanied by jumps. These effects are qualitatively similar to those produced by microinjections of SR 95103 (a GABA-A receptor antagonist) at the same site. These findings suggest that, at both the level of the CG and the MH, gamma-aminobutyric acid (GABA) tonically inhibits a neuronal substrate involved in the generation of flight reactions.

Allylglycine↗

PubMed1986

A neuropharmacological study of the periventricular neural substrate involved in flight.

This paper reviews results obtained in experiments concerning the neurochemical characteristics of the substrate involved in the control of flight reactions and the induction of aversive effects in the rat. These experiments investigated the behavioural effects produced by microinjecting into the periaqueductal grey matter (PAG) or the medial hypothalamus (MH) compounds known to interfere with the functioning of some neurotransmitter systems known to exist in these structures. The data obtained show that: the activity of the substrate involved in the production of flight reactions is tonically inhibited by the release of GABA (gamma-aminobutyric acid); the behavioural reactions produced by microinjecting GABA antagonists can be clearly distinguished, depending on whether such drugs were injected into the PAG or the MH, despite the fact that jumps were produced from either level; behavioural effects, comparable to some extent to those produced by microinjections of GABA antagonists, can be obtained by injecting drugs which act on non-GABAergic neurochemical substrates, namely opioidergic or cholinergic systems; and behavioural effects, comparable to those produced by injecting GABA antagonists into the PAG, can be obtained by injecting such drugs into various sites located in other parts of the tectum such as the inferior colliculus or adjacent structures.

Animals↗

PubMed1985

Behavioral effects of microinjections of SR 95103, a new GABA-A antagonist, into the medial hypothalamus or the mesencephalic central gray.

The behavioral effects of unilateral microinjections of SR 95103, a new GABA-A receptor antagonist, into periventricular structures were studied. When injected into the medial hypothalamus (MH) or into the dorsal part of the mesencephalic central gray (CG), SR 95103 produced a dose-dependent behavioral activation together with jumps. However, the characteristics of this behavioral activation differed according to whether SR 95103 was injected into the MH or into the CG. The behavioral activation was found to be attenuated by pretreatment with THIP, a GABA receptor agonist. When injected into the CG or into the deep layers of the superior colliculus, SR 95103 proved to affect the rat's reactivity to tactile stimuli as evidenced by ipsilateral 'neglect' combined with contralateral hyperreactivity expressed as withdrawal reactions and jumping. Similar results were obtained following microinjections of bicuculline methiodide at the same sites. These data confirm that in both the MH and the CG, GABA-A receptors are involved in the neural control of the generation and/or expression of aversive effects. The data further suggest that at the level of the CG and the deep layers of the superior colliculus, GABA is also involved in the gating of sensory information towards the substrate underlying the generation of such aversive effects.

Animals↗

PubMed1985

The effects of progabide (SL 76002) on locomotor activity and conditioned place preference induced by d-amphetamine.

The effect of prior treatment with a GABA mimetic, SL 76002 (100 mg/kg i.p.), on amphetamine-induced locomotor activity and conditioned place preferences with amphetamine (1.5 mg/kg i.p.) was investigated. SL 76002 significantly attenuated the motor stimulant effects of amphetamine, without influencing the rewarding properties at least as determined by the place preference procedure. When injected alone, SL 76002 did not affect handling-induced locomotor activation, nor did it exhibit any aversive or reinforcing properties. The results suggest that separate neural systems may subserve the motor and rewarding properties of amphetamine.

Animals↗

PubMed1984

Flight induced by infusion of bicuculline methiodide into periventricular structures.

Microinjections of different doses of bicuculline methiodide (BM) were performed into the mesencephalic central gray (CG), the medial hypothalamus (MH) and lateral hypothalamus (LH). Flight reactions could be induced by microinjections of BM into either the CG or the MH. However, the type of flight behavior was different whether the injection was made in the CG or the MH. Furthermore, microinjections of 35 ng of BM in either structure produced an increase in locomotor activity whose time course differed according to the injected structure, and an increase in rearings was induced at MH but not at CG sites. At lateral hypothalamic sites, BM produced an increase in locomotor activity and rearings but no jump. These effects were antagonized in a dose-dependent manner by a local pretreatment with 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), a GABA agonist. These results suggest that (1) at the level of both the MH and the CG, a GABAergic link is involved in the inhibition of a substrate whose activation produces aversive effects, and (2) the aversive effect induced by CG BM microinjection seems to be different from that induced by MH BM microinjection.

Animals↗

PubMed1983

Unilateral injection of GABA agonists in the superior colliculus: asymmetry to tactile stimulation.

A unilateral microinjection of each one of three different GABA agonists (Muscimol: 1.4 nmoles; Baclofen: 0.8 nmole; THIP: 10.7 nmoles) into the superior colliculus was found to result in a reversible asymmetry in the rat's responsiveness to tactile stimulation. The rat was hyporeactive to stimulations applied contralaterally and hyperreactive to stimulations applied ipsilaterally to the infusion site. Furthermore, the rat showed ipsiversive turning in response to tactile stimulation applied either ipsi- or contralaterally to the infusion site. The results are discussed in relation with motor and sensory asymmetry produced by unilateral manipulations affecting the striato-nigro tectal system.

Analgesics↗

PubMed1982

[Implication of gamma-aminobutyric acid (GABA) at the mesencephalic central gray level, in the elaboration of flight responses].

In the rat, a microinjection of bicuculline methiodide (0.03 to 0.065 nmole) into the mesencephalic central gray (GC) provokes a flight response. At a lower dose, it reduces - or increases - the latency with which the rat switches off an electrical stimulation applied to the GC. This latency is regularly increased by a local microinjection of muscimol. These results suggest that a GABAergic link within the GC is involved in the generation of an aversive effect and of the flight response which may express it.

Aggression↗

PubMedDate not supplied

Myoclonic and tonic seizures elicited by microinjection of cholinergic drugs into the inferior colliculus.

The inferior colliculus (IC) is the initiation site in the neuronal network for the epileptic audiogenic seizure (AGS). The present study investigates the effects of alteration of IC cholinergic transmission on the elicitation of epileptic seizures. Unilateral microinjections of carbachol (3 and 6 micrograms/0.2 microliter) into the IC elicited intense locomotor activity, contraversive rotations and myoclonic seizures. This result indicates that the IC is the initiation site for the induction of myoclonic seizures and suggests that these myoclonic seizures may result from activation of m1 muscarinic receptors. Microinjections of the nicotinic-muscarinic antagonist, gallamine (2 and 6 micrograms/0.2 microliter), into the IC induced AGS susceptibility. However, microinjections of muscarinic antagonists, atropine (15 micrograms/0.2 microliter) and scopolamine (12 and 20 micrograms/0.2 microliter), or the nicotinic antagonist, hexamethonium (12 and 20 micrograms/0.2 microliter), into the IC have no effect. Gallamine-induced AGS susceptibility may result from a selective blockade of m2 muscarinic receptors.

Acetylcholine↗