Lesion of the ventral tegmental area amplifies stimulation-induced Fos expression in the rat brain.

Unilateral lesions of the ventral tegmental area (VTA), the key structure of the mesolimbic system, facilitate behavioral responses induced by electrical stimulation of the VTA in the contralateral hemisphere. In search of the neuronal mechanism behind this phenomenon, Fos expression was used to measure neuronal activation of the target mesolimbic structures in rats subjected to unilateral electrocoagulation and simultaneously to contralateral electrical stimulation of the VTA (L/S group). These were compared to the level of mesolimbic activation after unilateral electrocoagulation of the VTA (L group), unilateral electrical stimulation of the VTA (S group) and bilateral electrode implantation into the VTA in the sham (Sh) group. We found that unilateral stimulation of the VTA alone increased the density of Fos containing neurons in the ipsilateral mesolimbic target structures: nucleus accumbens, lateral septum and amygdala in comparison with the sham group. However, unilateral lesion of the VTA was devoid of effect in non-stimulated (L) rats and it significantly amplified the stimulation-induced Fos-immunoreactivity (L/S vs S group). Stimulation of the VTA performed after contralateral lesion (L/S) evoked strong bilateral induction of Fos expression in the mesolimbic structures involved in motivation and reward (nucleus accumbens and lateral septum) and the processing of the reinforcing properties of olfactory stimuli (anterior cortical amygdaloid nucleus) in parallel with facilitation of behavioral function measured as shortened latency of eating or exploration. Our data suggest that VTA lesion sensitizes mesolimbic system to stimuli by suppressing an inhibitory influence of brain areas afferenting the VTA.

Chronic electric stimulation of the midbrain ventral tegmental area increases spleen but not blood natural killer cell cytotoxicity in rats.

Previously we found that in conscious, freely behaving rats chronic electric stimulation of the lateral hypothalamus (LH) caused significant augmentation of natural killer cell cytotoxicity (NKCC) and a large granular lymphocyte (LGL) number more pronounced in the spleen than in the peripheral blood. The LH belongs to the so-called "brain reward system", a collection of the central structures whose activation produce positive emotions. The midbrain ventral tegmental area (VTA) is another prominent reward-relevant structure. In the present work, chronic electric stimulation of VTA (constant current 0.1 ms duration cathodal pulses delivered at frequency 50 Hz during 60 min daily session for 14 consecutive days) caused in rats an increase in the spleen but not in the peripheral blood NKCC (chromium release assay) without simultaneous effect on the number of large granular lymphocytes (LGL) (morphological method) and plasma level of prolactin (PRL), growth hormone (GH), corticosterone (COR), and testosterone (TST). This effect was anatomically specific as no influence of analogous thalamic stimulation on immune and endocrine response was found. The results obtained indicate that both reward-related areas VTA and LH enhance the cell-mediated immune response, represented by natural killer cytotoxicity, especially in the spleen. However, the effect pronounced by VTA is weaker than that of LH, possibly due to additional connections of LH with the hormonal and/or autonomic control systems.

The effects of lateral hypothalamic lesions on peripheral blood natural killer cell cytotoxicity in rats hyper- and hyporesponsive to novelty.

Individual variability in the central control of the cellular immune responses is the main subject of the study. Previously, it was found that destruction of the lateral hypothalamus (LH) produced long-term depression of the cytotoxicity of NK cells (NKCC) and their number (LGL). In the present experiment we compared changes in the peripheral blood NKCC, LGL number, as well as leukocyte and lymphocyte number, their mitogenic activity and plasma corticosterone level evoked by electrolytic LH lesions in rats which were categorized as either high (HR) and low (LR) responders according to their locomotor response to a new environment. It was found that: (1) before the lesion NKCC (measured by 51Cr release assay) was higher in the HRs than in LRs; (2) LH damage caused a drop in NKCC and LGL number (21st postlesion day) preceded by a transient enhancement (5th postlesion day) significant for HRs only. As a result of a greater decrease in the HRs than LRs the baseline differences between groups disappeared by 21st postlesion day; (3) NKCC and LGL depression was not accompanied by changes in lytic activity of a single NK cell (agarose assay) which indicates that NKCC decrease concerned the population level and was dependent on LGL redistribution and/or recycling rate; (4) on the 21st postlesion day there was a significant leuko- and lymphopenia in the lesioned groups both HRs and LRs; (5) proliferative lymphocyte response to PWM (colorimetric assay) and plasma corticosterone level were not affected either by the motility level or by the lesion. The results emphasize the importance of individual differences in behavioral reactivity for NKCC regulation and a possible involvement of LH in the mechanism which connects high locomotor activity with stimulation of NKCC.

Chronic electrical stimulation of the lateral hypothalamus increases natural killer cell cytotoxicity in rats.

Previously, we found that in rats coagulation of the lateral hypothalamus (LH) caused depression of the peripheral blood natural killer cell cytotoxicity (NKCC) and the number of large granular lymphocytes (LGL). In the present work, we have tested the effects on both spleen and blood NKCC of acute (1 day) and chronic (21 days) electrical stimulation of LH, and LGL number in conscious, freely behaving animals. Five groups of male Wistar rats were used: LH stimulated (n=22), thalamic (Thal) stimulated control (n=4), operated but non-stimulated LH sham controls (n=7), non-operated normal control group (n=8) and spleen baseline group (n=10). Chronic stimulation of LH caused significant augmentation of NKCC (51Cr-release assay) and LGL number (a morphological method), more pronounced in the spleen than in the peripheral blood. Rats responding to LH stimulation with feeding showed a slightly greater effect than those responding with a locomotor reaction. The observed effects were anatomically specific as no influence of Thal stimulation or the sham procedure was found. The results are discussed in terms of the involvement of LH in reward phenomena and the hormonal control of the immune system.