The effect of diazepam on hippocampal EEG in relation to behavior.

Male mice of the BALB/cByJ and C57BL/6 strains were implanted with electrodes in the CA1 area of the hippocampus to record rhythmic slow-wave activity (RSA) or 'theta' EEG activity. The EEG spectral characteristics and the animal's motor behavior were studied while the animals walked on a moving belt (2.2 cm/s) both before and after i.p. injections of diazepam (Valium, 2 mg/kg) or vehicle. EEG spectral analyses were carried out on-line by computer. Diazepam produced a dissociation of locomotion and RSA. (1) Uninjected and vehicle-injected mice showed typical RSA (7-8 Hz) while walking. (2) Under diazepam, 7-8 Hz RSA virtually disappeared and was replaced in the temporally averaged records by RSA with a sharp, narrow-band peak at 4-5 Hz. (3) This lower-frequency RSA was associated with immobility if, and only if, the immobility immediately followed walking. This was true whether the animal itself stopped walking or the experimenter stopped the moving belt. This theta activity predominated for about 30 s and had disappeared after 2 min. Locomotion, on the other hand, was accompanied by irregular EEG activity. (4) Scopolamine (i.p. 1 mg/kg), a cholinergic blocker, greatly reduced the diazepam-induced 4-5 Hz RSA, but also partially restored 7-8 Hz RSA. The possibility that the effects of diazepam on hippocampal EEG involve changes in septohippocampal cholinergic activity is discussed.

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.

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.

Hippocampal stimulation limits performance but does not retard acquisition of food-reinforced learning.

Facilitation of the usually very slow acquisition of hippocampal (HPC) self-stimulation (SS) by prior, non-contingent HPC stimulation may be due to the progressive attenuation of a disruptive effect of the stimulation on learning. We attempted to answer two questions: (1) Does HPC stimulation disrupt food-reinforced learning when it follows each lever-press as in SS experiments? (2) Does prior exposure to the stimulation attenuate any such disruptive effect? We observed no significant differences in the rate of acquisition when each food-reinforced response was paired contingently with a 0.5 sec train of dorsal HPC stimulation (CS group), or when 0.5 sec trains were administered randomly throughout the session (RS), compared with an implanted control group (IC). Although acquisition was rapid in all groups, performance on the second day was significantly lower in the CS group than in the IC animals. These same electrode placements later supported SS. The same results were obtained with 3 similarly-treated groups that had previously received a program of daily HPC stimulation (kindling). The results imply that kindling does not produce its facilitating effect on acquisition of HPC SS by removing a disruptive effect of the stimulation.

[Differentiation of the effects of diazepam on self-stimulation behavior as a function of the structure of the stimulated brain]. / Différentiation des effets du diazépam sur le comportement d'autostimulation en fonction de la structure cérébrale stimulée.

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.

Differential effects of diazepam (valium) on brain stimulation reward sites.

The effect of diazepam on electrical self-stimulation of the dorsolateral hippocampus was tested in 19 male rats. Two mg/kg of diazepam significantly suppressed lever pressing rates at both high and low current intensities, whereas 1 mg/kg did so only at the low current intensity. The lowest dose (0.5 mg/kg) of diazepam had no significant effect. The second experiment tested the generality of the effect of diazepam on self-stimulation using electrodes in the lateral hypothalamus. A significant increase in lever pressing rates was observed at all dose levels.