Injections of picrotoxin and bicuculline into the amygdaloid complex of the rat: An electroencephalographic, behavioural and morphological analysis

Turski, Waldemar A.; Cavalheiro, Ésper A.; Calderazzo‐Filho, Lineu S.; Kleinrok, Z; Czuczwar, S.J.; Turski, Lechosław

doi:10.1016/0306-4522(85)90162-9

Cited by 67 publications

(21 citation statements)

References 54 publications

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“…The different observations might be related to strain differences. In agreement with our observation, however, doses higher than 300 ng/side had to be applied to the amygdala to induce the slightest seizure grade in Wistar rats in an animal model of temporal lobe epilepsy (Turski et al 1985).…”

Section: Discussionsupporting

confidence: 89%

Hyperactivity, decreased startle reactivity, and disrupted prepulse inhibition following disinhibition of the rat ventral hippocampus by the GABAA receptor antagonist picrotoxin

2001

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Rationale: Functional imaging studies have revealed overactivity of the hippocampus in schizophrenic patients. Neuropathological data indicate that hyperactivity of excitatory hippocampal afferents and decreased hippocampal GABA transmission contribute to this overactivity. In rats, excitation of the ventral hippocampus, e.g. by NMDA, results in hyperactivity and disruption of sensorimotor gating measured as prepulse inhibition (PPI) of the acoustic startle response, behavioral effects related to psychotic symptoms in humans.Objective: The present study examined whether disinhibition of the ventral hippocampus by the GABA A antagonist picrotoxin would result in similar psychosis-related behavioral disturbances (hyperactivity, decreased PPI) as NMDA stimulation. Methods and results: Wistar rats received bilateral infusions of subconvulsive doses of picrotoxin (100 or 150 ng/0.5 µl per side) into the ventral hippocampus and were then immediately tested for open field locomotor activity or startle reactivity and PPI. Only the higher dose induced hyperactivity and decreased PPI. Both doses decreased acoustic startle reactivity to a similar extent. The decreased PPI appeared not to result from decreased startle reactivity, but was associated with a diminished potency of the prepulses to inhibit the startle reaction to the startle pulse, indicating a sensorimotor gating deficit. All effects were temporary, i.e. disappeared when the rats were tested 24 h after infusion. Conclusions: Decreased GABAergic inhibition in the ventral hippocampus of rats yielded psychosis-related behavioral effects, very similar to those induced by NMDA stimulation. Thus, a concurrence of decreased GABAergic inhibition and increased afferent excitation in the hippocampus of schizophrenic patients might contribute to psychotic symptoms.

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Section: Discussionsupporting

confidence: 89%

Hyperactivity, decreased startle reactivity, and disrupted prepulse inhibition following disinhibition of the rat ventral hippocampus by the GABAA receptor antagonist picrotoxin

2001

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“…This led us to test the effect of a double dose. When treated with the higher gabazine dose (8 mg l −1 ), the low-CO 2 fish showed slightly higher activity during the first two behaviour trials (empty tank and novel object) relative to the low-CO 2 fish treated with 4 mg l −1 gabazine, consistent with what has previously been shown for high doses of GABA receptor blockers (Turski et al, 1985). However, during the final two behaviour trials ( predator and conspecifics), when gabazine levels in the 8 mg l −1 -treated fish were likely to have fallen closer to those of the 4 mg l −1 -treated fish during the first 10 min, activity of the low-CO 2 gabazine-treated fish was reduced by approximately 50% relative to the non-treated fish, to levels not statistically different than those of the high-CO 2 fish (P>0.05; Fig.…”

Section: Results Behavioursupporting

confidence: 87%

Ambient CO2, fish behaviour and altered GABAergic neurotransmission: exploring the mechanism of CO2-altered behaviour by taking a hypercapnia dweller down to low CO2 levels

Regan

Turko

Heras

et al. 2016

Journal of Experimental Biology

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Recent studies suggest that projected rises of aquatic CO 2 levels cause acid-base regulatory responses in fishes that lead to altered GABAergic neurotransmission and disrupted behaviour, threatening fitness and population survival. It is thought that changes in Cl − and HCO 3 − gradients across neural membranes interfere with the function of GABA-gated anion channels (GABA A receptors). So far, such alterations have been revealed experimentally by exposing species living in low-CO 2 environments, like many oceanic habitats, to high levels of CO 2 (hypercapnia). To examine the generality of this phenomenon, we set out to study the opposite situation, hypothesizing that fishes living in typically hypercapnic environments also display behavioural alterations if exposed to low CO 2 levels. This would indicate that ion regulation in the fish brain is fine-tuned to the prevailing CO 2 conditions. We quantified pH regulatory variables and behavioural responses of Pangasianodon hypophthalmus, a fish native to the hypercapnic Mekong River, acclimated to high-CO 2 (3.1 kPa) or low-CO 2 (0.04 kPa) water. We found that brain and blood pH was actively regulated and that the low-CO 2 fish displayed significantly higher activity levels, which were reduced after treatment with gabazine, a GABA A receptor blocker. This indicates an involvement of the GABA A receptor and altered Cl − and HCO 3 − ion gradients. Indeed, Goldman calculations suggest that low levels of environmental CO 2 may cause significant changes in neural ion gradients in P. hypophthalmus. Taken together, the results suggest that brain ion regulation in fishes is fine-tuned to the prevailing ambient CO 2 conditions and is prone to disruption if these conditions change.

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“…BMI was dissolved and diluted in 0.9% sodium chloride (SAL) immediately before use. It was administered bilaterally at a dose of 10 pmol in a volume of 0.5 l. The dose of BMI selected is well below doses that have been found previously to induce convulsion and brain seizure activity (Turski et al, 1985;Sanders and Shekhar, 1991;Dickinson-Anson and McGaugh, 1997). MDZ (Gobbi Novag, Buenos Aires, Argentina) was diluted in distilled water [vehicle (VEH)] and given intraperitoneally at the dose of 0.5 mg/kg, 20 min before either restraint exposure or intra-amygdaloid injection of BMI.…”

Section: Methodsmentioning

confidence: 99%

Previous Stress Facilitates Fear Memory, Attenuates GABAergic Inhibition, and Increases Synaptic Plasticity in the Rat Basolateral Amygdala

Manzanares¹,

Isoardi²,

Carrer³

et al. 2005

J. Neurosci.

230

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In experiments designed to investigate the relationship between stress and the acquisition of new fear memories, it was found that previous exposure to a restraint session increased fear conditioning in a contextual fear paradigm. Moreover, the infusion of bicuculline, a competitive antagonist of GABA A receptors, into the basolateral amygdala complex (BLA), but not into the central amygdaloid nucleus, induced the same behavioral effect. Pretreatment with midazolam (MDZ), a positive modulator of GABA A sites, prevented the facilitating influence on fear memory of both stress and GABA A receptor blockade in the BLA. These data suggest that facilitation of fear conditioning could be causally related to increased neuronal excitability attributable to depressed GABAergic inhibition in the BLA. To test this hypothesis, evoked potentials were studied in brain slices from stressed animals. Potentials evoked in the BLA by single stimuli applied to the external capsule showed multispike responses, suggestive of GABAergic disinhibition. These multiple responses were no longer evident after the slices were perfused with diazepam or if the stressed animals were pretreated with MDZ. In slices from stressed rats, paired-pulse inhibition (GABA dependent) was suppressed. Also, in stressed animals, long-term potentiation (LTP) was induced with a single train of high-frequency stimulation, which did not induce LTP in control rats. Moreover, MDZ pretreatment prevented the facilitating influence of stress on LTP induction. All of these findings support the hypothesis that previous stress attenuates inhibitory GABAergic control in the BLA, leading to neuronal hyperexcitability and increased plasticity that facilitates fear learning.

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Injections of picrotoxin and bicuculline into the amygdaloid complex of the rat: An electroencephalographic, behavioural and morphological analysis

Cited by 67 publications

References 54 publications

Hyperactivity, decreased startle reactivity, and disrupted prepulse inhibition following disinhibition of the rat ventral hippocampus by the GABAA receptor antagonist picrotoxin

Hyperactivity, decreased startle reactivity, and disrupted prepulse inhibition following disinhibition of the rat ventral hippocampus by the GABAA receptor antagonist picrotoxin

Ambient CO2, fish behaviour and altered GABAergic neurotransmission: exploring the mechanism of CO2-altered behaviour by taking a hypercapnia dweller down to low CO2 levels

Previous Stress Facilitates Fear Memory, Attenuates GABAergic Inhibition, and Increases Synaptic Plasticity in the Rat Basolateral Amygdala

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