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A G Sadile

Publications and source records attributed to A G Sadile.

45 records · Page 3Linked to original sources
PubMed1989

Adrenocorticoid receptor binding in the rat hippocampus: strain-dependent covariations with arousal and habituation to novelty.

In order to investigate whether the genotype-dependent behaviour of the Naples high-(NHE) and low-excitability (NLE) rat strains was modulated by differences in the capacity of hippocampal adrenocorticoid receptors, a correlative analysis was made among behavioural scores from exposure to a Làt-maze and in vitro [3H]corticosterone hippocampal binding capacity in these rats and in their random-bred controls (NRB). As previously shown, NHE/NLE-rats differed markedly upon forced exposure to the maze, with the NRB group occupying an intermediate position. No differences were found in maximal binding capacity (Bmax) and dissociation constant (Kd), nor in the individual maximal binding capacity (IMBC) between the two strains, while both showed lower IMBC than NRB-rats. These results tend to exclude that the genetic differences in the behaviour of NHE/NLE-rats are due to distinct patterns in the adrenocorticoid binding capacity in the hippocampus (HPC). Moreover, the intrastrain correlative analysis among IMBC (in the whole HPC and in its dorsal and ventral portion) and the behavioural scores showed that (1) motor and emotional correlates of 'arousal' to novelty were positively correlated in NLE and negatively in NHE-, but not in NRB-rats; (2) a consistent correlation was found with the intertrial activity decrement (long-term habituation), which was negative in both strains, and it was positive in NRB-rats. These complex co-variations are envisioned as possibly due to the differential modulatory components of the activation and inhibition of novelty-induced arousal response. However, our findings support the hypothesized involvement of the HPC, where adrenocorticoid receptors are selectively concentrated, in the modulation of some adaptive behavioural responses.

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PubMed1988

The sequential hypothesis on sleep function. I. Evidence that the structure of sleep depends on the nature of the previous waking experience.

The sequential hypothesis on sleep function assumes that the information gathered by brain during the waking period is processed during sleep in two main steps occurring during synchronized sleep (SS) and, eventually, during paradoxical sleep (PS). To verify the main consequences of the hypothesis, i.e., (1) that SS is involved in brain information processing; and (2) that the structure of sleep is dependent on the nature of the previous waking experience, an experiment was designed involving rats exposed to a training session (two-way active avoidance) but failing to learn (NL), and rats left in their home cages in the same training room (C). The structure of sleep, determined by EEG techniques in the postacquisition period (3 hr), was different in NL rats in comparison to C rats, chiefly because SS episodes were markedly longer in the former group. A more detailed analysis indicated that, in NL rats, SS episodes not followed by PS increased their duration first, while those followed by PS became longer in the second half of the sleep period. Comparable results were obtained in the comparison of NL and C subgroups deprived of PS at the end of the acquisition period by chlomipramine treatment. The data support the sequential hypothesis and provide evidence for a primary role of SS in brain information processing.

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PubMed1988

The sequential hypothesis on sleep function. II. A correlative study between sleep variables and newly synthesized brain DNA.

The information acquired by brain during wakefulness (W) may be processed in two sequential steps occurring during synchronized sleep (SS) and paradoxical sleep (PS), respectively. On the assumption that brain molecules synthesized during the acquisition step undergo a comparable sleep processing, we have designed an experiment aimed at the verification of the sequential hypothesis. Groups of adult female Wistar rats received [3H-methyl] thymidine by intraventricular injection 30 min before being exposed to a 4 hr session of a two-way active avoidance training. Animals failing to achieve the learning criterion were further allowed a period of 3 hr during which they were left free to sleep, or were deprived of PS or of total sleep. Control rats were similarly treated, but were left in their home cages in the same training room during the period of acquisition. The results of correlative study among behavioral, sleep and biochemical variables demonstrate that the specific radioactivity of DNA in the cerebral cortex, cerebellum and brainstem is correlated with several variables of postacquisition sleep, mostly SS parameters. The correlations depend on the previous waking experience of the rats. The data substantiate the two main consequences of the hypothesis, i.e., (1) the involvement of SS in brain information processing; and (2) the dependence of the operations performed by the sleeping brain on the nature of the previous waking experience. The results also provide some insight into the kind of processing which occurs in the sleeping brain.

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PubMed1987

Strain-specific correlations between hippocampal structural traits and habituation in a spatial novelty situation.

The rat strains Naples high-excitable (NHE) and Naples low-excitable (NLE) have been selectively bred since 1976 for behavioral arousal in a spatial novelty situation. The Timm-stained hippocampi of 20 NHE and 18 NLE rats were examined morphometrically for differences in the proportions (volume percentages) of terminal fields in the fascia dentata and CA3/CA4 at the mid-septotemporal level. Prior to histology animals were tested on 2 days for exploratory activity in a square alley system (Làt box). Overall, the two strains differed significantly in the percentage of stratum lacunosum molecular (NHE greater than NLE, P less than 0.001), of the intra/infrapyramidal mossy fiber (IIP-MF) projection (NLE greater than NHE, P less than 0.001), of the granule cell layer (NLE greater than NHE, P less than 0.05) and of the outer molecular layer (NHE greater than NLE, P less than 0.05). Both strains had an IIP-MF projection smaller than in any other rat strain. Most of the strain differences, however, appear to reflect genetic drift rather than a response to selective breeding. Unexpectedly, the highly active line (NHE) showed a strong correlation between the IIP-MF and overnight habituation; the larger the IIP-MF projection, the lesser the long-term habituation (r = -0.70, P less than 0.001). In the NLE rats, the IIP-MF correlated positively with overnight habituation (though not significantly, because of an outlier). In both lines, stratum oriens was negatively correlated with short-term habituation in the second exposure (NHE: r = -0.68, P less than 0.001; NLE: r = -0.66, P less than 0.01). Thus, hippocampal variability of non-genetic origin appears to be correlated with processes which modulate strain-characteristic responses to a spatial novelty situation.

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PubMedDate not supplied

Prenatal elevation of endocannabinoids corrects the unbalance between dopamine systems and reduces activity in the Naples High Excitability rats.

Several evidences suggest that endocannabinoids exert a neurotrophic effect on developing mesencephalic dopamine neurons. Since an altered mesocorticolimbic system seems to underlie hyperactivity and attention deficit in clinical and animal studies of attention deficit hyperactivity disorder (ADHD), prenatal elevation of anandamide has been induced in Naples high excitability (NHE) rats by inhibition of its reuptake. To this aim, pregnant NHE and random-bred females received a subcutaneous injection of AM-404 (1 mg/kg) or vehicle daily from E11 until E20. Young adult male offsprings were exposed to a spatial novelty (Làt-maze) for 30 min and the behavior was videotaped and analysed for indices of activity (travelled distance, rearing frequency) and attention (rearing duration). Moreover, morphological analysis of the brains was carried out that pertained to cytochrome oxydase as marker of metabolic activity and thyrosine hydroxylase as marker of the dopamine systems. The results indicate that prenatal AM-404 treatment significantly reduces activity by about 20% during the entire testing period and modifies the distribution of scanning times towards short duration episodes in the first part of the test only in NHE-treated rats. In addition, image analysis revealed a significant increase in relative optical density of TH+terminals in the dorsal striatum and substantia nigra of AM-404 treated NHE rats and minor changes in the dorsal cortex of AM-404 treated NRB rats. The data suggest a corrected unbalance between the two dopamine systems that apparently leads to reduced hyperactivity and modified scanning times in this animal model of ADHD. This, in turn, might open new strategies in the treatment of a subset of ADHD cases.

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PubMedDate not supplied

What can genetic models tell us about behavioral plasticity?

Biological diversity and learning have played an essential interactive role in the evolution of species, as intra-specific individual differences have exerted a buffering effect towards environmental changes, and learning ability per se has allowed their maintenance. By exploiting biological diversity individuals with defective learning and memory have been produced that allow the study of the neural substrates of encoding mechanisms, as has been done in studies from Drosophila to rodents. Various aspects of this neurogenetic approach are reviewed and pitfalls are indicated. It is clear that genetic models need to be implemented by an integrated multidisciplinary top-down approach based on behavioral, electrophysiological, histochemical, immunocytochemical and neurochemical techniques. Examples are presented from some animal models that illustrate how a systems level analysis of the neural substrates of information processing can be carried out using such an integrated scheme.

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