Cellular imaging with zif268 expression in the rat nucleus accumbens and frontal cortex further dissociates the neural pathways activated following the retrieval of contextual and cued fear memory

Quantitative in situ hybridization revealed that the expression of the plasticity-associated gene zif268 was increased in specific regions of the rat frontal cortex and nucleus accumbens following fear memory retrieval. Increased expression of zif268 was observed in neurons in the core of the nucleus accumbens during the retrieval of contextual and discrete cued fear associations. In contrast, zif268 expression was additionally induced in neurons of the nucleus accumbens shell and the anterior cingulate cortex during the retrieval of contextual but not cued fear memories. No changes in the expression of this gene were seen in the ventral medial prefrontal cortex or ventral and lateral regions of the orbitofrontal cortex that were correlated specifically with the retrieval of fear memory. These experiments demonstrate the specific and dissociable activation of limbic cortical-ventral striatal regions that accompanies cued and contextual fear. These data, together with those previously published by our laboratory (Hall, J., Thomas, K.L. & Everitt, B.J. (2001) J. Neurosci., 21, 2186-2193), suggest that retrieval of contextual fear memories activates a wider limbic cortical-ventral striatal neural circuitry than does retrieval of cued fear memories. Moreover, the expression of zif268 may contribute to plasticity and reconsolidation of fear memory in these dissociable pathways.     

Organization of the ascending projections from the ventral tegmental area: a multiple fluorescent retrograde tracer study in the rat

The projections from the ventral tegmental area of Tsai (VTA) to the frontal cortex (FC), lateral septum (LS), were investigated in the rat by means of the double retrograde fluorescent tracer technique. True blue and fast blue were used in combination with nuclear yellow as retrograde tracers. After combined injections placed into two different terminal fields, many singly and some doubly labeled neurons were seen in the midbrain. In all cases the labeled cells were observed in the ipsilateral VTA, while after injections placed into the LS and Acc some fluorescent neurons were also seen in the contralateral VTA. The patterns of distribution of the labeled neurons showed a topographic organization of the VTA efferent pathways. However, some degree of overlapping was evident in the distribution of cells retrogradely labeled from different terminal fields. The number of the doubly labeled neurons varied according to the sites of combined injections, but in each experiment it never exceeded 10% of the total number of labeled perikarya. Doubly labeled neurons were particularly numerous after combined injections placed into the FC, LS, or LH; on the contrary, very few doubly labeled cells were observed after combined injections placed into the CPu and LS or LH. The organization of the ascending VTA projections suggests that they are probably integrated into different anatomical sets.     

Demonstration of synaptic input from prefrontal cortex to the habenula in the rat

Using lesion-degeneration techniques at the EM level, it is confirmed that a pathway from prefrontal cortex projects to the lateral habenula, and further that it makes synaptic contacts predominantly with dendrites of neurons in the medial sector of the lateral nucleus.The available neuroanatomical evidence points to a role for habenula as a regulator of the activity of the meso-cortical dopamine pathway by the interaction of this cortico-habenular pathway with a wide variety of limbic inputs in the medial sector of lateral habenula.     

Opposite changes in dopamine utilization in the nucleus accumbens and the frontal cortex after electrolytic lesion of the median raphe in the rat

As revealed by the changes in dihydroxyphenylacetic acid (DOPAC) levels and in the DOPAC/Dopamine (DA) ratio, DA utilization was markedly enhanced in the nucleus accumbens and reduced in the prefrontal cortex of rats five days after the electrolytic lesion of the median raphe. These opposite effects were not seen any more seventeen days after the lesion. These results suggest that neurones originating from the median raphe and projecting to the ventral tegmental area exert an opposite effect on the activity of DA cells innervating the nucleus accumbens and on those projecting to the prefrontal cortex.     

Expression of Fos-related antigens in the nucleus accumbens and associated regions following exposure to a cocaine-paired environment

This study examined whether conditioned hyperactivity measured in a cocaine-paired environment was associated with increased expression of Fos-related antigens (FRA) within the nucleus accumbens (NAc) and associated forebrain regions of rats. Three groups of rats were given repeated injections of either cocaine in the test environment and saline in the colony room (group Paired), saline in the test environment and cocaine in the colony room (group Unpaired), or saline in both environments (group Control). All rats were subsequently given a drug-free test for conditioned hyperactivity in the test environment, and their brains were removed so that FRA immunohistochemistry could be conducted. Rats in the Paired group showed conditioned hyperactivity during the conditioning test, and this behavioural response was associated with increased FRA expression within the caudal NAc, the medial prefrontal cortex and the lateral septum relative to the Unpaired and Control groups. Paired rats also showed increased FRA expression within the orbital prefrontal cortex, the claustrum, the caudal amygdala (basolateral and central regions), the paraventricular thalamic nucleus, the subiculum of the hippocampus, and the lateral habenula relative to the Control group. However, the FRA levels in these latter sites were not significantly increased relative to those of Unpaired rats, indicating that genomic responses in these regions were not entirely context dependent. The correspondence between conditioned hyperactivity and enhanced FRA expression within the caudal NAc, the medial prefrontal cortex and lateral septum suggests that these regions may participate in the expression of conditioned responses to cocaine-related stimuli.     

Electrophysiological identification of mesencephalic ventromedial tegmental (VMT) neurons projecting to the frontal cortex, septum and nucleus accumbens

The electrophysiological properties of neurons located in the mesencephalic ventromedial tegmentum (VMT) and the organization of the efferents of these neurons to the frontal cortex, the septum, the nucleus accumbens and the head of the striatum were studied in ketamine-anesthetized rats. The projections of the VMT cells were determined through use of the antidromic activation method. Our results show that VMT projections to different target areas originate mainly from different VMT neurons. However, in some cases single VMT neurons were found to send axon collaterals to two different areas. Three branching patterns were observed: septum-cortex, septum--nucleus accumbens and septum--striatum. The occasional observation of temporally distinct antodromic responses from a single area was considered to result from activation of different branches of the arborizing axon. The distribution of antidromic response latencies for VMT projections to each structure is discussed in relation to the question of dopaminergic versus non-dopaminergic mesolimbic and mesocortical systems.     

Prenatal nicotine exposure alters neuroanatomical organization of the developing brain

Although there has been considerable research conducted regarding the long‐term effects of prenatal exposure to nicotine, there has been little examination of how this experience influences brain development. This study was designed to examine if there are morphological changes (dendritic branching, dendritic length, and spine density) in medial prefrontal cortex, orbital frontal cortex, parietal cortex, and nucleus accumbens associated with exposure to nicotine during gestation. Nicotine or saline was administered to pregnant Long Evans dams for the duration of pregnancy. Golgi‐Cox techniques were used to examine neuroanatomy of offspring at postnatal day 21. The dendritic changes identified in rats exposed to nicotine prenatally resembled neuroanatomical changes that are identified in rats administered with nicotine in adulthood. Of the 18 anatomical parameters measured, 11 exhibited significant modification, with two parameters apical and basilar spine density in parietal cortex demonstrating sex‐dependent modification. These early changes in anatomy and behavior have important implications for later plasticity and long‐term well‐being. Synapse 66:950–954, 2012. © 2012 Wiley Periodicals, Inc.     

Cytoarchitecture and cortical connections of the posterior cingulate and adjacent somatosensory fields in the rhesus monkey

The cytoarchitecture and connections of the caudal cingulate and medial somatosensory areas were investigated in the rhesus monkey. There is a stepwise laminar differentiation starting from retrosplenial area 30 towards the isocortical regions of the medial parietal cortex. This includes a gradational emphasis on supragranular laminar organization and general reduction of the infragranular neurons as one proceeds from area 30 toward the medial parietal regions, including areas 3, 1, 2, 5, 31, and the supplementary sensory area (SSA). This trend includes a progressive increase in layer IV neurons. Area 23c in the lower bank and transitional somatosensory area (TSA) in the upper bank of the cingulate sulcus appear as nodal points. From area 23c and TSA the architectonic progression can be traced in three directions: one culminates in areas 3a and 3b (core line), the second in areas 1, 2, and 5 (belt line), and the third in areas 31 and SSA (root line). These architectonic gradients are reflected in the connections of these regions. Thus, cingulate areas (30, 23a, and 23b) are connected with area 23c and TSA on the one hand and have widespread connections with parieto-temporal, frontal, and parahippocampal (limbic) regions on the other. Area 23c has connections with areas 30, 23a and b, and TSA as well as with medial somatosensory areas 3, 1, 2, 5, and SSA. Area 23c also has connections with parietotemporal, frontal, and limbic areas similar to areas 30, 23a, and 23b. Area TSA, like area 23c, has connections with areas 3, 1, 2, 5, and SSA. However, it has only limited connections with the parietotemporal and frontal regions and none with the parahippocampal gyrus. Medial area 3 is mainly connected to medial and dorsal sensory areas 3, 1, 2, 5, and SSA and to areas 4 and 6 as well as to supplementary (M2 or area 6m), rostral cingulate (M3 or areas 24c and d), and caudal cingulate (M4 or areas 23c and d) motor cortices. Thus, in parallel with the architectonic gradient of laminar differentiation, there is also a progressive shift in the pattern of corticocortical connections. Cingulate areas have widespread connections with limbic, parietotemporal, and frontal association areas, whereas parietal area 3 has more restricted connections with adjacent somatosensory and motor cortices. TSA is primarily related to the somatosensory-motor areas and has limited connections with the parietotemporal and frontal association cortices.     

Organization of amygdaloid projections to the mediodorsal thalamus and prefrontal cortex: a fluorescence retrograde transport study in the rat

Previous studies have shown that the amygdala projects to both the mediodorsal thalamic nucleus (MD) and its cortical projection area, the prefrontal cortex (PFC). In this investigation rats received injections of different fluorescent retrograde tracers (true blue and diamidino yellow) into MD and either the lateral, polar, or medial PFC in order to examine the relationship of amygdaloid neurons with cortical and/or thalamic projections. PFC injections labeled neurons in the basolateral (BL), basomedial (BM), ventral endopiriform (EnV), and rostral lateral nuclei as well as the periamygdaloid cortex (PAC) and the medial part of the amygdalohippocampal area (AHA). In BL, which contained the great majority of neurons projecting to PFC, most labeled cells were concentrated in particular parts of the nucleus and were topographically organized. The overwhelming majority of labeled neurons in BL were large pyramidal or piriform cells that correspond to class I neurons described in Golgi studies. Occasional small neurons with thin dendrites were also observed; these cells may be class II neurons. MD injections labeled numerous cells in the anterior division of the cortical nucleus, medial nucleus, and caudomedial part of the central nucleus. Moderate numbers of labeled cells were found in caudal portions of BM and PAC, whereas scattered cells were observed throughout the rest of the amygdala with the exception of the lateral nucleus. In BL and AHA many MD-projecting neurons were observed along nuclear boundaries and in the adjacent white matter. Neurons in BL, BM, and AHA usually had large elongated or irregular somata and two to four primary dendrites that branched sparingly. Other cells had smaller ovoid somata. The morphology and distribution of MD-projection cells in the basolateral amygdala indicate that they are primarily large class II neurons. Double-labeled amygdaloid neurons, labeled by both cortical and thalamic injections, were observed only in a small number of animals. Control experiments suggest that most of the double-labeled cells in these cases were artifacts caused by spread of the thalamic injectate into the third ventricle with subsequent uptake by fibers in the anterior commissure. Thus the findings of this study suggest that different neuronal populations in the amygdala project to the two poles of the MD-PFC system. In the basolateral amygdala class I neurons are the predominant cell type involved in PFC projections, whereas a subpopulation of class II neurons, hitherto thought to be primarily local-circuit neurons, project to MD.     

Reconsolidation‐induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens

Systems consolidation is a time‐dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization‐dependent mechanism interpreted as reconsolidation, that restored the normal course of systems consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation‐induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1‐anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying systems consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reconsolidation‐driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of systems consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.     

Blockade of ovulation and release of LH in the rat by electrochemical stimulation of the frontal lobe cortex

The effect of stimulation of the frontal lobe cortex on the release of luteinizing hormone (LH) and ovulation was studied in female rats. Electrochemical stimulation (anodic DC) was applied through monopolar stainless-steel electrodes chronically implanted in the non-anesthetized freeely-behaving animals bearing plastic cannula inserted into the jugular vein for blood sampling.In rats, on the day of proestrus, stimulation (100 uA/30 sec) of the medical cortical surface in the superficial and deep layers of the medial precentral area and of the anterior cingulate area blocked ovulation in about 80% of the animals. A similar effect was seen when the stimulus was applied in the deep layers of the prelimbic and infralimbic areas. On the contrary, stimulation in the superficial layers of these latter two areas, as well as in the superficial and deep layers of the restrospenial cortex, did not affect normal ovulation. The preovulatory discharge of LH was blocked in the animals which failed to ovulate. The degree of inhibition exerted by the anterior cingulate area and the prelimbic area on ovulation and LH surge was proportional to the amount of current applied.Stimulation of the anterior cingulate area also blocked the release of LH induced by the injection of progesterone into ovariectomized estrogen-primed rats. Furthermore, electrochemical stimulation of the anterior cingulate area inhibited the rise of LH in the serum induced by electrical stimulation of the medial preoptic area of ovariectomized estrogen-injected rats, but it failed to affect that resulting from electrical stimulation of the medial basal hypothalamus.On the other hand, stimulation of the lateral cortical surface and the ventral cortex of the frontal lobe on the day of proestrus affected normal ovulation and LH surge only when the stimulus was applied in the agranular insular area which also exhibited an inhibitory action.It is concluded that certain areas of the frontal lobe cortex related to limbic structures exert an inhibitory influence on ovulation and LH secretion.     

Localized lesions of arcopallium intermedium of the lateral forebrain caused a handling-cost aversion in the domestic chick performing a binary choice task

Behavioral effects of handling cost (time and/or energetic cost for food consumption) on choice were examined using domestic chicks trained in operant task reinforced by delayed food rewards. When scattered sesame was delivered in more demanding conditions, a colored cue bead associated with six grains ('large' and 'costly' reward) was chosen progressively less frequently against another bead associated with one grain ('small' and 'not costly' reward). The choice thus proved to be highly sensitive to the anticipated handling cost. Excitotoxic lesion of the bilateral arcopallium intermedium also selectively reduced the choice of the six grains, while leaving actual cost investment (number of pecks and handling time) unaltered. No significant changes occurred in choices between one grain of sesame ('small' and 'not costly' reward) and one grain of barley (or a ball composed of six sesame grains glued by starch; 'large' and 'not costly' reward), indicating that choice based on anticipated food amount was not impaired. On the other hand, lesion of the ventral striatum did not change the choice ratio in any trial types. Operant peck latencies somewhat depended on food rewards, but were not affected by lesions of the arcopallium or the ventral striatum. The arcopallium could contribute to foraging behaviors by enabling chicks to overcome the handling cost, thus gaining more beneficial food. Furthermore, the present results indicate doubly dissociated functional roles of the ventral striatum and the arcopallium, the former in the cost of traveling for food and the latter in the cost of handling food, respectively.     

Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of alpha2-adrenergic and serotonin2C receptors: a comparison with citalopram

Mirtazapine displayed marked affinity for cloned, human alpha2A-adrenergic (AR) receptors at which it blocked noradrenaline (NA)-induced stimulation of guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]-GTPgammaS) binding. Similarly, mirtazapine showed high affinity for cloned, human serotonin (5-HT)2C receptors at which it abolished 5-HT-induced phosphoinositide generation. Alpha2-AR antagonist properties were revealed in vivo by blockade of UK-14,304-induced antinociception, while antagonist actions at 5-HT2C receptors were demonstrated by blockade of Ro 60 0175-induced penile erections and discriminative stimulus properties. Mirtazapine showed negligible affinity for 5-HT reuptake sites, in contrast to the selective 5-HT reuptake inhibitor, citalopram. In freely moving rats, in the dorsal hippocampus, frontal cortex (FCX), nucleus accumbens and striatum, citalopram increased dialysate levels of 5-HT, but not dopamine (DA) and NA. On the contrary, mirtazapine markedly elevated dialysate levels of NA and, in FCX, DA, whereas 5-HT was not affected. Citalopram inhibited the firing rate of serotonergic neurons in dorsal raphe nucleus, but not of dopaminergic neurons in the ventral tegmental area, nor adrenergic neurons in the locus coeruleus. Mirtazapine, in contrast, enhanced the firing rate of dopaminergic and adrenergic, but not serotonergic, neurons. Following 2 weeks administration, the facilitatory influence of mirtazapine upon dialysate levels of DA and NA versus 5-HT in FCX was maintained, and the influence of citalopram upon FCX levels of 5-HT versus DA and NA was also unchanged. Moreover, citalopram still inhibited, and mirtazapine still failed to influence, dorsal raphe serotonergic neurons. In conclusion, in contrast to citalopram, mirtazapine reinforces frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission. These actions reflect antagonist properties at alpha2A-AR and 5-HT2C receptors.     

Region-specific response of the hippocampus to chronic unpredictable stress

The objective of the present study was to determine whether chronic unpredictable stress (CUS) would induce hippocampal neuroplasticity in a region-specific manner. Recent evidence suggests that the hippocampus has two functionally distinct subsections. The dorsal (septal) portion appears to be primarily associated with spatial navigation, while the ventral (temporal) region has been linked to affect-related functions, such as anxiety. Chronic stress has previously been shown to negatively affect the hippocampus by decreasing survival of progenitor cells, although it has also been shown to increase adaptive responses, such as increased expression of neuropeptide Y (NPY) and ΔFosB. Whether such events occur in a region-specific manner has not been investigated. We hypothesized that CUS would selectively impact cell survival, NPY, and ΔFosB expression in the more affect-related ventral subregion. Individually housed Long-Evans rats (n = 31) were divided into two groups: stressed and control. Stressed animals were exposed daily to an unpredictable schedule of ethologically relevant stressors, such as predator odors, forced swim, and open field exposure. All rats were injected with bromodeoxyuridine (BrdU) daily during the first 5 days of CUS in order to label dividing progenitor cells. Unbiased stereology was used to quantify BrdU+, NPY+, and ΔFosB+ cells in dorsal and ventral hippocampal subregions. In support of our hypothesis, we found that CUS selectively decreased cell survival in the ventral subregion. However, both NPY and ΔFosB were significantly increased only in the dorsal hippocampus. These results suggest that stress-induced adaptive neuroplasticity occurs primarily in the dorsal subregion, which may coincide with behavioral aspects of the stress response, such as avoidance or amelioration of the stressor.     

Interlaminar astroglia of the cerebral cortex: a marker of the primate brain

Evidence for "cable-like" processes stemming from astroglial cells in the supragranular cerebral cortex has been recently presented. In addition to what could be called the "general mammalian-like" astroglial architecture (the so-called "panglial syncytium") of the cerebral cortex, composed of typical stellate astrocytes (intralaminar astrocytes), the anthropoid species, mostly catarrhines, show a manifest vertical, radial distribution of long (interlaminar) astroglial processes. It can be tentatively proposed that evolutionary pressures resulted in the progressive appearance, in primates, of a new type of glial cell. Its soma has a superficial location and unusually long cellular processes that invade, in a predominant radial fashion, the supragranular region of the cerebral cortex. Their existence has been ignored for more than a century. On the neuronal side, modular (columnar) organization of the cerebral cortex may represent an evolutionary acquisition that could optimize communication and information processing, with the least volume compromise in terms of wiring. Yet, for such columns to be functionally operative, adequate isolation from neighboring units would be required. A "mass" operation of the astroglial architecture would tend to compromise spatial definition and the degrees of freedom of such columnar modules. It is proposed that the presence of a "palisade" of interlaminar glial processes represents a relatively recent evolutionary event, instrumental for the optimization of the modular (columnar) organization of the cerebral cortex. It is interesting that the supragranular cortical region has undergone the largest growth among mammalian species during brain evolution, and has been associated with a crucial role in cortico-cortical interactions.     

Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys

The intrinsic cortico-cortical connections within the orbital and medial prefrontal cortex (OMPFC) were demonstrated with retrograde and anterograde tracers injected into each of the architectonic areas that constitute this region. Although many of the connections linked neighboring areas, others selectively connected relatively distant areas. Most, but not all, of the connections were reciprocal. Altogether, the connections formed at least two distinct networks within the OMPFC. The “orbital” prefrontal network linked most of the areas within the orbital cortex, with very few connections to medial prefrontal areas. Areas Iam, Iapm, Ial, 121, 12m, and 12r in the caudal and lateral parts of the orbital cortex (which received inputs from several sensory modalities) had convergent connections with areas 13l, 13m, and 13b in the central orbital cortex, with further connections to the rostral orbital area 11l. For the connections between areas Iapm, Iam, Ial, 13m, 13l, and 11l, rostrally directed fibers arose mainly in layer V, whereas caudally directed fibers originated mainly in layer III. The “medial” prefrontal network selectively involved medial areas 14r, 14c, 24, 25, 32, and 10m, rostral orbital areas 10o and 11m, and agranular insular area Iai in the posterior orbital cortex. Two orbital areas, 13a and 12o, had substantial connections to both networks and may serve as points of interaction between them; otherwise there were relatively few interconnections. The two networks also had distinct connections with other cortical regions, with limbic structures, and with the mediodorsal thalamic nucleus. Their role in guidance of affective behavior is discussed. © 1996 Wiley-Liss, Inc.     

Expression of brain Gi protein in the aging F344 rat following exposure to corticosterone

G protein expression has been shown to be modulated by circulating plasma corticosterone in young animals. A loss of G protein expression regulation by corticosterone in the elderly could explain declines in the function of G protein-coupled receptors and their effective signal transduction processes in the nervous system found in normal and pathological aging. In this study, adrenalectomized 3- and 18-months-old female Fischer 344 rats were exposed to low, moderate or high levels of plasma corticosterone to determine the effect of this hormone on G_i protein expression in the hippocampus and frontal cortex. Basal G_i protein expression, assessed by Western blot analysis, did not vary across age in either brain region. Hippocampal G_i protein levels increased following moderate and high corticosterone administration in the 3-months old animals (125% ; P < 0.05) but not in the 18-months old animals. In contrast, in the frontal cortex, G_i protein expression increased significantly in the 18-months-old group (93% ; P < 0.05) following exposure to high concentrations of corticosterone. These results suggest that steroid hormones, specifically corticosterone, may differentially modulate neurotransmitter-G protein coupling in an age-dependent manner.     

Differential adaptive properties of accumbens shell dopamine responses to ethanol as a drug and as a motivational stimulus

Non-adaptive activation of dopamine transmission in the nucleus accumbens shell by drugs of abuse has been attributed a fundamental role in the mechanism of drug addiction. In order to test this hypothesis, we compared in the same subject the effect of an addictive drug (ethanol) and of taste stimuli, including ethanol's own taste, on dialysate dopamine in the nucleus accumbens shell as an estimate of dopamine transmission and on taste reactivity as an expression of motivational valence. Ethanol was also monitored in the dialysates. In naive rats, intraoral infusion of a 20% sucrose + chocolate solution elicited a monophasic increase of dialysate dopamine immediately after the intraoral infusion. In contrast, intraoral infusion of 10% ethanol, 10% ethanol + 20% sucrose or 10% ethanol + 20% sucrose + chocolate solutions elicited a biphasic increase of nucleus accumbens dopamine with an early taste-related rise and a late rise related to dialysate ethanol. Pre-exposure to the ethanol solutions 24 h before resulted in the absence of the early dopamine rise and permanence of the late dopamine rise. This late dopamine rise was actually increased as compared with that of the nonpre-exposed group when sucrose-containing ethanol solutions were tested. The results indicate that single trial pre-exposure to the ethanol solutions differentially affects the responsiveness of nucleus accumbens shell dopamine to the direct intracerebral action of ethanol and to the effect of its taste with potentiation, or no change of the first and abolition of the second. These observations point to the existence of major differences in the adaptive regulation of nucleus accumbens dopamine transmission in the shell after drug as compared with taste reward. These differences, in turn, are consistent with a role of nucleus accumbens shell dopamine in the mechanism of the behavioural effects of addictive drugs.     

Brain Structure and Task-specific Increase in Expression of the Gene Encoding Syntaxin 1B During Learning in the Rat: A Potential Molecular Marker for Learning-induced Synaptic Plasticity in Neural Networks

The mRNAs encoding the synaptic vesicle proteins syntaxin 1 B and synapsin I were measured using in situ hybridization in several brain regions-the dentate gyrus, CA3 and CA1 of the hippocampus, the parietal, the motor and prefrontal cortices and the core and shell of the accumbens-of rats that were learning a spatial reference or working memory task on a radial arm maze. The mRNA encoding syntaxin 1B was significantly increased in all hippocampal regions in rats learning the working memory task, whereas it was increased in the prelimbic area of the prefrontal cortex and the shell of the accumbens in rats learning the spatial reference memory task. No change in mRNA encoding syntaxin 1B was observed in the motor and parietal cortices or the core of the accumbens, and the mRNA encoding synapsin I was not significantly different from that of naive caged controls or rats running the maze for continuous reinforcement in any of the brain structures examined. These results demonstrate that the gene encoding a key member of synaptic vesicle function is up-regulated in a task- and brain-specific manner during learning. They are discussed in terms of the potential role this protein may play in trans-synaptic propagation of plasticity within specific neural networks as a function of the information required in the laying down of different types of memory.