Effect of 5-HT in mianserin-pretreated rats on the structure of feeding behavior.

The present study examined the effects of intra-PVN serotonin injection in mianserin-pretreated rats at the onset of the dark phase of light cycle on the structure of feeding behavior. The drugs were injected into the paraventricular nucleus (PVN) of the hypothalamus. The animals were maintained in a self-selection feeding paradigm and provided with freely available and separate sources of protein, carbohydrate, fat and water. The suppressive effect of 5-HT on carbohydrate intake was attenuated by mianserin at the beginning of the active (dark) feeding period. Mianserin-pretreatment increased the duration of carbohydrate and protein intake, but it was unable to block the effect of 5-HT on meal frequency and local rate of carbohydrate consumption. The present data suggests that carbohydrate intake may be in part mediated by postsynaptic 5-HT(2A/2C) receptors. However, the temporal characteristics of carbohydrate ingestion are mediated by another subpopulation of 5-HT receptors in the PVN and indicates a possibly adrenergic influence.

One-trial tolerance to midazolam is due to enhancement of fear and reduction of anxiolytic-sensitive behaviors in the elevated plus-maze retest in the rat.

The anxiolytic-like effects of benzodiazepines (BZDs) in rats is reduced after a single exposure to the elevated plus-maze test (EPM). Several hypotheses have been formulated but no conclusive explanation exists for this phenomenon called "one-trial tolerance." In this study, we examined this phenomenon further by carrying out an ethopharmacological analysis of the behavior of rats submitted to the EPM in two trials. Rats injected with saline before both trials (control), treated with 1.0 mg/kg of midazolam before both trials (MM), or only before Trial 2 (SM), were exposed to the EPM. The SM group did not differ from the controls in the Trial 1 and Trial 2 conditions. The MM group showed a clear anxioselective profile in Trial 1 and no anxiolytic-like effects in Trial 2. Whereas midazolam injected before the first trial caused no significant change in immobility, there was a pronounced increase in immobility during Trial 2 for all three conditions. These data suggest that the anxiolytic-like action of midazolam in the first trial gives way to the fear-related insensitive behaviors (phobic/avoidance responses) responsible for the one-trial tolerance to BZDs in Trial 2. Furthermore, an additional experiment showed that midazolam does not seem to affect the acquisition of the learned avoidance response since it is present upon retesting even after midazolam administration in Trial 1 (MS group). Rather, the present data suggest an emotional shift from Trial 1 to Trial 2, which leads to change in the responsiveness of the animals to BZDs.

Effects of central muscarinic blockade on passive avoidance: anterograde amnesia, state dependency, or both?

It was recently reported that administration of relatively high intensities of footshock (overreinforcement) during training of passive avoidance protected animals against the amnesic effect of scopolamine, injected 5 min after training. This was interpreted in terms of a lesser involvement of acetylcholine in memory consolidation. An alternative explanation was that overreinforcement accelerated the consolidation process, which could have taken place before the injection of scopolamine. To test for this possibility, male Wistar rats were injected with 4, 8, or 12 mg/kg of scopolamine, 5 min before training with low or high levels of footshock and then tested for retention of the task. Scopolamine induced the expected memory deficit after the low-intensity footshock; after overreinforcement the higher doses of scopolamine induced state dependency, while no deficits were produced with the lower dose. It was concluded that: (a) acetylcholine is indeed involved in memory consolidation of passive avoidance; (b) scopolamine interacts with high footshock levels to produce state dependency; and (c) when relatively low doses of scopolamine are used in conditions of overreinforcement, protection against scopolamine-induced amnesia becomes evident.

Intrastriatal injection of choline accelerates the acquisition of positively rewarded behaviors.

The prediction was made that by increasing the synthesis of striatal acetylcholine, through local injection of its precursor choline, the acquisition of a lever-pressing response in two different autoshaping situations would be accelerated. In the first experiment, choline was injected into the striatum or parietal cortex of rats immediately after dipper training; 24 h later and during 5 consecutive days the animals were submitted to an autoshaping procedure of the operant kind. In the second experiment, choline was administered to the same regions shortly after each of three classical-operant autoshaping sessions; during the next two sessions, autoshaping contingencies of the operant kind were in effect. In both experiments choline injection into the striatum induced a marked facilitation of acquisition of the conditioned responses, although cortical injection of choline produced a milder improvement only in the first experiment. These results indicate that striatal cholinergic activity is, indeed, involved in the early phases of positively reinforced learning.

Protective effect of under-reinforcement of passive avoidance against scopolamine-induced amnesia.

Administration of antimuscarinic drugs induces amnesia of aversively motivated behaviors. However, when relatively high intensities of footshock are used during training (over-reinforcement), animals become protected against such amnesic state. Moreover, the protective effect is established in a none-or-all fashion, i.e., within a series of increasing intensities a minute augmentation of footshock intensity is sufficient to reach the protective threshold. In the present experiment it was found that very low intensities of aversive stimulation (under-reinforcement), sufficient to produce learning, also protected animals from scopolamine-induced amnesia. These results suggest that acetylcholine is critically involved in memory consolidation of passive avoidance, but only within a limited range of training intensities.

Effects of GABA antagonists on inhibitory avoidance.

Experimental data indicate that GABA is involved in memory processes. However there are marked inconsistencies in the reported effects of interference with GABA synaptic activity on memory consolidation of aversively-motivated tasks. Both amnesia and improvement of performance have been reported after treatment with GABA antagonists. These contradictory effects could be explained by procedural differences in training. To test for this possibility rats were trained in passive avoidance using two levels of footshock and injected with a wide range of doses of picrotoxin and bicuculline. Picrotoxin did not modify the conditioned response while bicuculline induced amnesia only with the lower doses at both low and high footshock intensities. It was concluded that GABA is involved in memory consolidation, and that the conflicting results in the literature are indeed due, in part, to procedural differences, and also to the mode of action of these drugs.

A threshold for the protective effect of over-reinforced passive avoidance against scopolamine-induced amnesia.

Acetylcholine-receptor blockers produce amnesia of aversively motivated behaviors. However, when animals are submitted to relatively high intensities of footshock (over-reinforcement), anticholinergic treatment does not induce memory impairments. The aim of this work was to determine whether the antiamnesic effect produced by increasing the magnitude of the negative reinforcer is gradually established or if a threshold should be reached to obtain such an effect. Wistar rats were trained in passive avoidance using 2.5, 2.6, 2.7, 2.8, 2.9 or 3.0 mA; 5 min after training they were given one systemic injection of scopolamine (8 mg/kg). An amnesic state was produced in the groups that were trained with the lower intensities (2.5-2.7 mA); with the three higher intensities near-perfect retention was evident. These results suggest that acetylcholine is critically involved in memory consolidation, and that by increasing the magnitude of the negative reinforcer, a threshold is reached where cholinergic activity of the nervous system is not necessary for the development of the consolidation process.

Time-dependent effects of cholinergic blockade of the striatum on memory.

Rats were trained on a passive avoidance task, and a retention test was carried out 24 h later. Scopolamine was injected into the anterior striatum at one of various intervals following training: at 2 min it produced amnesia; an intermediate degree of impairment was found when given 8 min after training. With a delay of 15 min, this drug did not produce an interference with memory. These observations suggest that striatal cholinergic activity is involved in memory consolidation.

Is acetylcholine involved in memory consolidation of over-reinforced learning?

Systemic administration of anticholinergic drugs produces amnesia. To determine whether this effect can be prevented by increasing the magnitude of the learning experience, independent groups of rats were trained in passive avoidance, using a 3.0-mA footshock, and then injected with scopolamine (2, 4, 6, 8 or 12 mg/kg). When retention of the task was evaluated, a dose-dependent amnesic effect was found. When footshock intensity was increased to 6.0 and 9.0 mA, injections of 8 and 12 mg/kg of scopolamine did not produce memory impairments. These findings indicate that acetylcholine plays an important role in consolidation of passive avoidance, but it does not seem to be involved in memory processes when the magnitude of the negative reinforcer is increased.

Mating produced analgesia in the Syrian hamster.

A series of experiments examined the hypothesis that mating produced analgesia in the Syrian hamster can be blocked by opiate antagonists. The first experiment established a dose response relation to painful footshock. Females were more responsive to footshock than males (p less than 0.001). The second experiment demonstrated that ten minutes of mating reduced responsiveness of both males and females to a moderate intensity of footshock. The third experiment replicated the effect of mating on the responsiveness of males to footshock, but did not demonstrate any effect of the opiate antagonist naltrexone on mating induced analgesia. The fourth experiment demonstrated that limited mating stimulation (five intromissions) has little effect on the responsiveness of sexually inexperienced males to footshock. The fifth experiment replicated the fourth experiment using sexually experienced males and obtained comparable results. Apparently mating induced analgesia in male hamsters is not blocked by opiate antagonists and which raises questions about biological activity of reported changes in endorphin activity during mating.

Differential effects of cholinergic blockade of anterior and posterior caudate nucleus on avoidance behaviors.

Groups of rats were trained in a one-trial passive avoidance task and then tested for retention 24 and 48 h later. They were also trained, in a single session, according to a one-way active avoidance paradigm. The effects of microinjections of atropine or of saline into the anterior caudate nucleus (CN) and of atropine into the posterior CN were assessed on these conditioned responses. Only those rats injected with atropine in the anterior CN showed a retention deficit in passive avoidance, while no effects on active avoidance became evident in any of the groups. These results suggest that cholinergic activity of the anterior CN is critically involved in memory consolidation of passive avoidance, but not in the processes mediating the acquisition of relatively simple active avoidance learning.

Early neuronal alterations caused by experimental thinner inhalation in young rats.

Young rats were treated with thinner inhalations (50 and 100 p.p.m., v/v). The brains of treated and control animals were studied with standard techniques of light and electron microscopy and with ultrastructural cytochemical method for localization of RNA. No alterations were found in the group treated with a single session of inhalation, irrespective of the dose. Animals treated with 10 or 20 sessions showed altered neurons in cerebral cortex, caudate nucleus, hypothalamus and cerebellar cortex. More frequent alterations were: small nucleoli with loss of their reticular structure and a marked decrease of their normal granular component; diminution of perichromatin fibrils and of ribosomes. In the animals treated with high doses of thinner (20 sessions, 100 p.p.m.) a small number of neurons show an increased amount of lysosomes, autophagosomes and neurofibrillar hypertrophy. These results suggest that thinner inhalation causes an initial impairment of gene transcription and of RNA processing followed by neuronal degeneration.