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P Cazala

Publications and source records attributed to P Cazala.

At least 37 records · Page 2Linked to original sources

Self-stimulation behavior can be elicited from various 'aversive' brain structures.

Electrical stimulation applied to various brain regions of the negative motivational system: the dorsal part of the mesencephalic central gray area (CG) the medial hypothalamus (MH), the medial lemniscus (ML), the lateral tegmentum (LT) and the reticular formation (RF), produces vigorous escape responses in mice. In spite of their highly aversive consequences, stimulation of all these regions also elicits self-stimulation behavior. This paradoxical approach response was clearly observed when the animals were placed in a Y-maze where they could successively trigger and turn off continuous electrical stimulation. In effect, mice stimulated in 'aversive' structures, similarly to animals stimulated in the lateral hypothalamus (LH), were able to discriminate between the reinforced arm and the non-reinforced arm of the Y-maze in order to self-administer the stimulation. When the mice were placed in a lever press box which delivered 0.2 s of electrical stimulation, an evident self-stimulation behavior was observed in LH and in some animals implanted in RF or MH. On the other hand, the very low response rates recorded in CG, LT, ML and in other RF or MH implanted mice do not permit a description of the motivational properties of these different stimulation sites. These results show that stimulation of brain structures of the negative reinforcement system has an approach component which, however, shows up clearly only in certain experimental situations.

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Lesion of the temporo-ammonic perforant path facilitates self-stimulation of the lateral entorhinal cortex in mice.

The effect of a lesion of the perforant path (PP) on self-stimulation (SS) of the lateral entorhinal cortex (LEC) was tested in mice between 8 and 21 days after surgery. The current intensities tested ranged between 0 and 80 microA (peak to peak 100 Hz sine-wave). The PP lesion led to a two-fold increase in SS rates at intensities above 30 microA without affecting the baseline SS rates (0 microA) and SS threshold (30 microA). The lesion also led to a significant increase in LEC after-discharge (AD) threshold and eliminated behavioral convulsions during SS testing. The suppression of AD by i.p. Na phenobarbital injection (10 mg/kg) led to a similar increase in SS rates in sham-lesioned mice; there was no difference in PP-lesioned animals. These results might be interpreted as evidence in favor of an independence of the neuronal processes mediating entorhinal and hippocampal reward-related behaviors.

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Self-stimulation of an 'aversive' brain structure: the mesencephalic central gray area.

Four experiments were performed in BALB/c mice implanted either in the lateral hypothalamus (LH) or in the dorsal part of the mesencephalic central gray area (CG) or both in LH and CG. In the first 3 experiments the animals were placed in a Y-maze where they could successively trigger and turn off continuous electrical stimulation. Expt. 1 showed that mice stimulated in CG (like animals stimulated in LH) are able to discriminate between the reinforced and the non-reinforced arm of the Y-maze in order to self-administer the stimulation. This behavior was observed whether the experimental situation was a simple spatial discrimination or a more complex light-dark discrimination. During the second experiment, the animals could choose between stimulation of low intensity (in one arm) or high intensity (in the other arm). We observed that, like LH animals, CG implanted mice chose the higher stimulation, despite its strong aversive component. On the other hand, Expt. 3 showed that when the animals could chose between CG stimulation, whose intensity was progressively increased, and LH stimulation whose intensity remained constant (low) they preferred the latter. When the mice were placed in a lever-press box where they could obtain 0.2 s of electrical stimulation (last experiment), LH animals showed vigorous self-stimulation behavior, whereas CG animals showed only a weak response rate. These results show that, in spite of its aversiveness, dorsal CG stimulation has an appetitive component whose magnitude may vary under different experimental conditions.

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Dissociation of limbic structures by pharmacological effects of diazepam on electrical self-stimulation in the mouse.

The effect of diazepam was tested on self-stimulation (SS) in 21 mice implanted with a bipolar electrode in the lateral hypothalamus (LH), the dorsolateral hippocampus (HPC) or the lateral entorhinal cortex (LEC). Diazepam, injected i.p. in doses of 0.5, 1 and 2 mg/kg, significantly increased SS rates with electrodes in LH while 4 and 8 mg/kg of diazepam had no significant effect. At low doses, similar increases were seen in mice with LEC electrodes but high doses produced a significant suppression. HPC animals showed an almost total suppression of SS beginning at 2 mg/kg of diazepam; lower doses had no significant effect. The results indicate that entorhinal and hippocampal SS are at least partly independent phenomena; in addition, the suppression of SS by moderate doses of diazepam remains specific to the HPC among the brain structures studied to date.

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Electrical self-stimulation of the mesencephalic central gray area: facilitation by lateral hypothalamic stimulation.

Three experiments were performed with BALB/c mice implanted both in the lateral hypothalamus (LH) and the dorsal part of the mesencephalic central gray area (CG). Initially, the effects of a brief electrical stimulation (0.2 sec) of the LH on approach and escape responses produced by continuous stimulation of the dorsal CG, were studied in a shuttle-box. Starting at an intensity of 10 microA, imposed LH stimulation both reduced approach latency and increased escape latency with CG stimulation. In the second and third experiments, the animals were placed in a standard self-stimulation (ICSS) box; depressions of a lever delivered brief electrical stimulations (0.2 sec). During the second experiment, it was observed that the very weak ICSS behavior produced by dorsal CG activation was greatly improved by forced LH stimulation. Finally, in the third experiment, simultaneous ICSS in LH and CG was compared with ICSS in LH alone. When low current intensities were used, simultaneous ICSS in LH and CG was more intense than ICSS in LH alone. These data especially suggest that dorsal CG stimulation has an appetitive component, and consequently that neuronal elements related to the positive reinforcement system are present in the dorsal CG area. Furthermore, the fact that one can obtain interactions between mesencephalic and hypothalamic ICSS is in accordance with the claim that the LH has connections with the CG area.

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[Differentiation of the effects of diazepam on self-stimulation behavior as a function of the structure of the stimulated brain].

The effect of diazepam was tested on self-stimulation in 21 mice with a bipolar electrode in lateral hypothalamus (HL), dorsolateral hippocampus (HPC) or lateral entorninal cortex (CEL). Diazepam at 0.5, 1 and 2 mg/kg significantly increased self-stimulation rates in HL while 4 and 8 mg/kg had no significant effect. Similar increases were seen in CEL mice but high doses produced a significant suppression. HPC animals showed a drastic suppression of self-stimulation beginning at 2 mg/kg of diazepam, lower doses having no significant effect. The results demonstrate that entorhinal and hippocampal self-stimulation involve at least partly independent neuronal mechanisms and point to a possible inhibitory influence of HPC and CEL.

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A Y-maze test reveals the positively reinforcing properties of electrical stimulation of the mesencephalic central gray area.

Animals stimulated in the dorsal part of the mesencephalic central gray area (CG) are able, as are animals stimulated in the lateral hypothalamus, to discriminate between the reinforced and the non-reinforced arm of an Y-maze to trigger a continuous electrical stimulation. This result clearly demonstrates that stimulation of the dorsal part of CG has an appetitive component.

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Central catecholamine metabolism and hypothalamic self-stimulation behaviour in two inbred strains of mice.

These experiments were conducted in order to better understand the role of catecholaminergic neurons in intracranial self-stimulation behaviour (ICSS) elicited from the lateral hypothalamus (LH). Two strains of mice which differ in their ICSS rate and their thresholds were studied. In a first time, we compared the catecholamine (CA) content and activity in various parts of the brain including cell bodies and nerve terminals of the man CA bundle. We used for this determination a high performance liquid chromatographic separation and an electrochemical detection. We observed that the BALB/c strain is distinguished by a higher CA activity than the DBA/2 strain. This correlates with a higher ICSS response rate in the BALB/c strain. The effects of stimulation on CA metabolism were then investigated, the electrodes being implanted specifically either in the dorsal or the ventral part of the LH and the biochemical data obtained analysed separately. Significant enhances of CA turn-over (TO) were noted in nerve terminals as hippocampus, cortex and accumbens. These results provide further evidence for the involvement of dorsal noradrenergic bundle and mesolimbic dopaminergic bundle in LH ICSS. Stimulation in the dorsal part of the LH produced the higher ICSS rate and seemed to induce a large variation of the CA TO. We noted also that the CA metabolism was always more altered in the DBA/2 than in the BALB/c strain, which is surprising in regard to the behaviour and remains unclearly explained.

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Effects of apomorphine, clonidine or 5-methoxy-NN-dimethyltryptamine on approach and escape components of lateral hypothalamic and mesencephalic central gray stimulation in two inbred strains of mice.

The effects of intraperitoneal injections of increasing doses of apomorphine, clonidine or 5-methoxy-NN-dimethyltryptamine (5-m-DMT) on approach and escape reactions induced by lateral hypothalamic (LH) or mesencephalic central gray (CG) stimulation were compared in BALB/c and DBA/2 mice. Apomorphine increased both the approach latency for LH stimulation and the escape latency for CG stimulation; the BALB/c strain was more reactive than DBA/2 animals. Clonidine reduced the approach latency for LH stimulation only in the BALB/c strain. 5-m-DMT increased escape latency both for LH and CG stimulation only in the DBA/2 strain. These results suggest that the neurochemical regulation of escape reactions respectively generated by LH or CG activation is partially different: dopamine seems to be involved only in CG aversion, whereas serotonin (5-HT) modulates both LH and CG escape reactions. Moreover, our results demonstrate a noradrenergic influence on the appetitive component of LH stimulation. Finally, they confirm that approach and escape reactions, particularly when induced from lateral hypothalamus, depend on distinct neuronal populations.

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Approach responses for mesencephalic central gray stimulation are facilitated by D-amphetamine or food deprivation.

The effects of either injection of D-amphetamine or food deprivation on approach and escape responses produced by continuous electrical stimulation of either the lateral hypothalamus (LH) or the dorsal part of the mesencephalic central gray area (CG), were studied in the DBA/2 strain of mice using the shuttle-box technique. Both D-amphetamine and food deprivation decreased approach latency for LH as well as for CG stimulation. Changes in escape latency were observed only for LH stimulation and only during the food deprivation test. These results suggest the involvement of positive reinforcement circuits along with dorsal CG activation.

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Effect of clonidine and phentolamine on self-stimulation behavior in the dorsal and ventral regions of the lateral hypothalamus in mice.

The effects of IP injections of increasing doses of clonidine and phentolamine on self-stimulation behavior (ICSS) in the dorsal and ventral regions of the lateral hypothalamus were studied in C57BL/6 mice. Clonidine specifically stimulates alpha-noradernergic receptors and has two distinct effects on ICSS. Ventral hypothalamic ICSS is immediately depressed at low doses (5 microgram/kg) whereas dorsal ICSS exhibits a discrete increase. At higher doses, ICSS is perturbed at both sites. Phentolamine is a specific blocking agent of alpha-noradrenergic receptors and depresses dorsal ICSS more than that of the ventral region. These observations clearly indicate a noradrenergic influence in the dorsal region of the hypothalamus.

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Effects of Lilly 110140 (flouxetine) on self-stimulation behavior in the dorsal and ventral regions of the lateral hypothalamus in the mouse.

The effects of Lilly 110141 (fluoxetine) injected IP on self-stimulation behavior triggered in the dorsal and ventral regions of the lateral hypothalamus were studied in C57BL/6 mice strain. Lilly 110140 inhibits serotonin reuptake. It depresses dorsal self-stimulation at a low dose (5 mg/kg) and improves ventral sel-stimulation at a high dose (20 mg/kg). The changes brought about by the injection of the 5 mg/kg dose support the proposed inhibitory role of serotonin on self-stimulation and also suggest that the fibers communicating with certain serotonergic neurons are localized primarily in the dorsal region of the lateral hypothalamus.

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The recombinant inbred strains: a tool for the genetic analysis of differences observed in the self-stimulation behaviour of the mouse.

The self-stimulation behaviour (ICSS) in the lateral hypothalamus of mice was studied using 5 recombinant inbred strains having the DBA/2 and BLAB/c lines for their parental origin. Two of these recombinant inbred strains behave like the recessive parental line (BALB/c) while the three others have a performance level similar to that of the dominant (DBA/2) parent. This division suggests that there is a major gene which determines the difference in performance between the two parental lines. The mean value for the self-stimulation threshold is negatively correlated with the value of the performance. The sensitivity to convulsions, which interrupt ICSS behaviour above certain current intensities, is under the control of a genetic determinant independent, but more complex, than the one which controls the level of performance.

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