tetrodotoxin and Amnesia

Acquisition of conditioned taste aversion (CTA) in rats is not prevented by functional decortication, anesthesia or hypothermia applied after intake of the flavored fluid and maintained throughout the action of the poison but is disrupted by bilateral application of 10 ng tetrodotoxin (TTX) into the parabrachial nuclei. The blockade is directly proportional to TTX dosage, indirectly proportional to distance of the injection site from parabrachial nuclei and equally affects CTAs using different CS (saccharin, NaCl) and different US (LiCl, carbachol, amphetamine, cycloheximide). CTA is disrupted by TTX applied up to 4 but not 8 days after a single CS-US pairing. TTX fails to disrupt overtrained CTA and elicits only a weak anterograde amnesia when applied 1 but 2 or more days before CTA acquisition. It is concluded that the parabrachial nuclei and the adjacent reticular formation probably represent the neural substrate of the permanent CTA engram the protracted consolidation of which is disrupted by prolonged cessation of impulse which is disrupted by prolonged cessation of impulse activity in the information storing network.

Topics: Amnesia; Animals; Avoidance Learning; Brain Stem; Conditioning, Classical; Rats; Tetrodotoxin

There is extensive evidence that amnestic treatments are less effective, or ineffective when administered to subjects that have been overtrained or subjected to high foot-shock intensities in aversively motivated learning. This protective effect has been found with a variety of learning tasks and with treatments that disrupt activity in several regions of the brain, including the hippocampus, amygdala, striatum, and substantia nigra. Such findings have been interpreted as suggesting that the brain regions disrupted are not critical sites for the memory processes induced by these types of training. In most experiments investigating this issue the amnestic treatments were administered after training. Thus, it might be less amnesia was induced because the training accelerated memory consolidation and, thus, the maximum effect of the amnestic treatment occurred after memory of the learning experience was consolidated. This study investigated this issue by inactivating the hippocampus of rats bilaterally with tetrodotoxin (TTX) (10 ng/side) 30 min before one-trial inhibitory avoidance training using relatively low (1.0 mA), medium (2.0 mA), or high (3.0 mA) foot-shock intensities. Retention of the task was measured 48 h after training. TTX produced a profound retention deficit, a mild deficit, and no deficit at all in the 1.0, 2.0, and 3.0 mA groups, respectively. These data confirm the protective effect of training with relatively high foot-shock intensity against experimentally induced amnesia, and suggests that this protection is not due to accelerated consolidation. Rather, the findings suggest that strong training activates brain systems other than those typically involved in mediating memory consolidation.

Topics: Amnesia; Animals; Avoidance Learning; Habituation, Psychophysiologic; Hippocampus; Male; Memory; Rats; Rats, Wistar; Sodium Channel Blockers; Tetrodotoxin

The cerebellum, amygdala and perirhinal cortex are involved in fear learning but the different roles that these three structures play in aversive learning are not well defined. Here we show that in adult rats amygdala or cerebellar vermis blockade causes amnesia when performed immediately, but not 1 h, after the recall of fear memories. Thus, the cerebellum, as well as the amygdala, influences long-term fear memories. These effects are long lasting, as they do not recover over time, even after a reminder shock administration. However, all of the subjects were able to form new fear memories in the absence of inactivation. By increasing the strength of conditioning, we observed that stronger fear memories are affected by the combined but not independent amygdala and cerebellar blockade. These results demonstrate that the cerebellum supports the memory processes even in the absence of a crucial site for emotions like the amygdala. Furthermore, they suggest that the amygdala is only one of the neural sites underlying long-term fear memories. Finally, the inactivation of the perirhinal cortex never alters retrieved fear traces, showing important differences between the amygdala, cerebellum and perirhinal cortex in emotional memories.

Topics: Amnesia; Amygdala; Animals; Anisomycin; Avoidance Learning; Cerebellum; Fear; Male; Memory; Nerve Net; Nerve Tissue Proteins; Neural Pathways; Parahippocampal Gyrus; Protein Synthesis Inhibitors; Rats; Rats, Wistar; Sodium Channel Blockers; Tetrodotoxin; Time; Time Factors

We examined the effect of KW-6055 [alpha-(p-butyrylamino-o-nitrobenzyl) pyridine], which has anti-amnesic activity, on the central cholinergic systems of rat frontal cortex using in vivo brain microdialysis. 1) KW-6055 (40, 160 mg/kg, p.o.) increased the extracellular level of ACh in normal rats (257 +/- 23, 202 +/- 24%). The stimulating effect of KW-6055 on ACh release was abolished by tetrodotoxin treatment, supporting that the released ACh was due to neuronal firing. Reserpine pretreatment decreased the effect of KW-6055, indicating that KW-6055 acted on cholinergic neurons through catecholaminergic neurons. 2) In basal forebrain-lesioned rats, KW-6055 (40 mg/kg, p.o.) significantly increased the extracellular level of ACh (251 +/- 22%) for more than 2 hr, which was longer than in normal rats. In conclusion, these results suggest that the stimulating activity on ACh release may be involved in the mechanism of the anti-amnesic effects of KW-6055.

Topics: Acetylcholine; Acetylcholinesterase; Amnesia; Animals; Cerebral Cortex; Male; Nitrobenzenes; Parasympathetic Nervous System; Pyridines; Rats; Rats, Wistar; Receptors, Muscarinic; Reserpine; Stimulation, Chemical; Tetrodotoxin

Tetrodotoxin (TTX; a voltage-sensitive sodium channel blocker) was microinjected bilaterally into the insular (IC), frontal (FC), or parietal (PC) cortex or the ventral caudate nucleus of rats either before or after they were trained in an inhibitory avoidance task. When administered either before or after training, injections of TTX into the IC impaired performance on a 48-hr retention test. Injections of TTX into the PC also impaired retention when administered before training. One week later, rats with cannulae in the IC, FC, and PC received microinjections of TTX either before or after training in a water maze (Morris) spatial learning task and retention was tested 24 hr later. TTX impaired retention when administered to the IC either before or after training. These findings indicate that a functionally intact IC during and after training in these tasks appears to be essential for the storage of long-term memory.

Topics: Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; Cerebral Cortex; Male; Microinjections; Rats; Rats, Inbred Strains; Spatial Behavior; Tetrodotoxin