Basal Forebrain Structures Research Articles

Anatomical Substrates of Behavioral Impairment Induced by Developmental Lead Exposure in Monkeys: Inferences from Brain Lesions

There is a substantial literature exploring the behavioral consequences of developmental lead exposure in the monkey; deficits have been observed on a number of tasks assessing learning and memory including spatial delayed alternation, discrimination reversal, matching to sample, and concurrent discrimination. Differences in performance between control and lead-exposed monkeys have also been observed on intermittent schedules of reinforcement. Comparison of the effects of lead with the extensive literature on the consequences of lesions in discrete areas of brain on the same tasks may provide insight into the possible sites of brain damage responsible for lead-induced behavioral impairment. Available data strongly suggest that prefrontal cortical areas are damaged by lead, based on the pattern of performance deficits across specific tasks. In addition, a constellation of global deficits including perseveration, increased distractibility, inability to change response strategy, and inability to inhibit inappropriate responding are hallmarks of both prefrontal damage and developmental lead exposure. Evidence also implicates basal forebrain structures in behavior impairment produced by lead based on the pattern of deficits across numerous tasks, although the evidence is much weaker than for prefrontal cortex. In contrast, the pattern of behavioral impairment produced by limbic system lesions is different in many respects from that produced by lead; in addition, the scant neuropathological data available suggest that limbic structures are not a target of lead even at high blood lead levels in the monkey. Comparison of the pattern of damage following lead exposure with the effects of lesions, presented here, provides direction for further morphological or neurochemical exploration of lead-induced brain damage in the monkey.

Selective Expression of Dopamine D3Receptor mRNA in Proliferative Zones during Embryonic Development of the Rat Brain

We studied by in situ hybridization histochemistry the expression of D3 receptor (D3R) mRNA at various stages of rat brain development. The first expression of D3R mRNA was detected at embryonic day 14 (E14) in the striatal and rhinencephalic neuroepithelia and throughout the tectal neuroepithelium. From E16 to E19 D3R mRNA expression extended along a rostrocaudal axis to additional proliferative ventricular zones of the basal forebrain, including the neuroepithelia of the olfactory bulb, nucleus accumbens, septum, and amygdala, whereas D1 and D2 receptor (D1R and D2R) mRNAs were expressed predominantly by migrating neuroblasts and/or differentiating striatal neurons. Only a few neuroblasts, migrating in the lateral cortical stream or developing as cerebellar Purkinje cells, expressed D3R mRNA from E18. At birth D3R expression mRNA appeared in differentiating neuronal fields of the nucleus accumbens and medial mamillary body primordia and on P5 reached a distribution similar to that found in adult. In addition, a transient upregulation was detected on P5 in the medial mamillary bodies, parietofrontal cortex, and olfactory tubercle. In the adult brain D3R gene expression continued in the striatal proliferative subventricular zone. The late expression D3R mRNA in neurons, after achievement of dopamine innervation, supports the existence of a regulating factor released from dopamine neurons, as suggested by denervation studies in the adult. The sustained and abundant D3R gene expression, predominantly in germinative neuroepithelial zones actively involved in neurogenesis of most basal forebrain structures, supports the hypothesis of a neurogenetic but minor morphogenetic modulatory role for the D3R during CNS development.

Implications of Immediate-Early Gene Induction in the Brain Following Sexual Stimulation of Female and Male Rodents

Induction of immediate-early genes (IEGs), such as c-fos, has been widely used to mark the activation of brain regions following different types of sexual stimulation and behavior. A relatively common set of hormone-concentrating basal forebrain and midbrain structures in female and male rodents is activated by copulatory stimulation, in particular, stimulation of sensory nerves that innervate the penis or vagina/cervix, olfactory or pheremonal stimuli, and conditioned sexual incentives. These regions include the preoptic area, lateral septum, bed nucleus of the stria terminalis, paraventricular hypothalamus, ventromedial hypothalamus, medial amygdala, ventral premammillary nuclei, ventral tegmentum, central tegmental field, mesencephalic central gray, and peripeduncular nuclei. Regions that do not contain classic intracellular steroid receptors, such as the ventral and dorsal striatum or cortex, are also activated. IEGs have also been colocalized with cytoplasmic proteins like GnRH and oxytocin, and have been used in conjunction with retrograde tracers to reveal functional pathways associated with different sexual behaviors. Steroid hormones can also alter the ability of sexual stimulation to induce IEGs. Despite the many similarities, some differences in IEG induction between sexes have also been found. We review these findings and raise the question of what IEG induction in the brain actually means for sexual behavior, that is, whether it indicates the perception of sexual stimulation, commands for motor output, or the stimulation of a future behavioral or neuroendocrine event related to the consequences of sexual stimulation. To understand the role of a particular activated region, the behavioral or neuroendocrine effects of lesions, electrical stimulation, drug or hormone infusions, must also be known.

Surgical management of giant pituitary tumours--a review of 30 cases.

An experience with surgical management of 30 giant pituitary tumours is analysed in this report. The clinical features, anatomical spread and relationship of these tumours with the cavernous sinus and other parasellar and basal forebrain structures is analysed. The problem encountered in the surgical treatment are reviewed. An unusual feature in the management was an intra-operative and post-operative tumour swelling and acute elevation of the intracranial pressure in 5 patients. Despite the technical problems encountered during surgery and in the post-operative period it was observed that a significant resection and adequate decompression of the visual apparatus offered a reasonable opportunity for recovery in vision and a satisfactory outcome. Complete resection of the tumour was not possible in this series. A contralateral subfrontal route was seen to be most suitable for resection of the part of the tumour that invaded the cavernous sinus.

Catecholamines and Indoleamines in the Central Nervous System of a Urodele Amphibian: A Microdissection Study with Emphasis on the Distribution of Epinephrine (Part 2 of 2)

Individual brain nuclei and regions of the central nervous system of adult male roughskin newts (Taricha granulosa) were microdissected and the concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid, dopamine, 5-hydroxyindoleacetic acid, and serotonin were determined using high performance liquid chromatography (HPLC) with electrochemical detection. The pattern of distribution of these catecholamines and indoleamines revealed many similarities between this urodele and other vertebrates. The highest concentrations of biogenic amines were observed in brainstem, hypothalamic, and basal forebrain structures; the lowest concentrations were observed in the internal granule layer of the olfactory bulb and pallial structures of the telencephalon. High concentrations of catecholamines and indoleamines were found in hypothalamic periventricular regions that are known to include cerebrospinal fluid-contacting, monoamine-containing neuronal cell bodies. The rostral diencephalon, which included the preoptic recess organ, had high concentrations of the primary catecholamines, norepinephrine and dopamine, and extremely high concentrations of the secondary catecholamine epinephrine. The dorsomedial infundibular hypothalamic region, which included the paraventricular organ, had high concentrations of dopamine and serotonin. The lateral infundibular hypothalamic region, which included the nucleus infundibularis dorsalis, had high concentrations of each of the biogenic amines. The results revealed unique patterns of distribution for each of the catecholamines and indoleamines studied, and provided evidence that regions of the hypothalamus that include cerebrospinal fluid-contacting, monoamine-containing neuronal cell bodies are focal regions for the metabolism of multiple biogenic amines.

Catecholamines and indoleamines in the central nervous system of a urodele amphibian: a microdissection study with emphasis on the distribution of epinephrine.

Individual brain nuclei and regions of the central nervous system of adult male roughskin newts (Taricha granulosa) were microdissected, and the concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid, dopamine, 5-hydroxyindoleacetic acid, and serotonin were determined using high performance liquid chromatography (HPLC) with electrochemical detection. The pattern of distribution of these catecholamines and indoleamines revealed many similarities between this urodele and other vertebrates. The highest concentrations of biogenic amines were observed in brainstem, hypothalamic, and basal forebrain structures; the lowest concentrations were observed in the internal granule layer of the olfactory bulb and pallial structures of the telencephalon. High concentrations of catecholamines and indoleamines were found in hypothalamic periventricular regions that are known to include cerebrospinal fluidcontacting, monoamine-containing neuronal cell bodies. The rostral diencephalon, which included the preoptic recess organ, had high concentrations of the primary catecholamines, norepinephrine and dopamine, and extremely high concentrations of the secondary catecholamine epinephrine. The dorsomedial infundibular hypothalamic region, which included the paraventricular organ, had high concentrations of dopamine and serotonin. The lateral infundibular hypothalamic region, which included the nucleus infundibularis dorsalis, had high concentrations of each of the biogenic amines. The results revealed unique patterns of distribution for each of the catecholamines and indoleamines studied, and provided evidence that regions of the hypothalamus that include cerebrospinal fluid-contacting, monoamine-containing neuronal cell bodies are focal regions for the metabolism of multiple biogenic amines.

Immunocytochemical distribution of catecholamine‐synthesizing neurons in the hypothalamus and pituitary gland of pigs: Tyrosine hydroxylase and dopamine‐β‐hydroxylase

This study describes the distribution of catecholaminergic neurons in the hypothalamus and the pituitary gland of the domestic pig, Sus scrofa, an animal that is widely used as an experimental model of human physiology in addition to its worldwide agricultural importance. Hypothalamic catecholamine neurons were identified by immunocytochemical staining for the presence of the catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine-β-hydroxylase. Tyrosine hydroxylase-immunoreactive perikarya were observed in the periventricular region throughout the extent of the third ventricle, the anterior and retrochiasmatic divisions of the supraoptic nucleus, the suprachiasmatic nucleus, the ventral and dorsolateral regions of the paraventricular nucleus and adjacent dorsal hypothalamus, the ventrolateral arcuate nucleus, and the posterior hypothalamus. Perikarya ranged from parvicellular (10–15 μm) to magnocellular (25–50 μm) and were of multiple shapes (rounded, fusiform, triangular, or multipolar) and generally had two to five processes with branched arborization. No dopamine-β-hydroxylase immunoreactive perikarya were observed within the hypothalamus or in the adjacent basal forebrain structures. Both tyrosine hydroxylase- and dopamine-β-hydroxylase-immunoreactive fibers and punctate varicosities were observed throughout areas containing tyrosine hydroxylase perikarya, but dopamine-β-hydroxylase immunoreactivity was very sparse within the median eminence. Within the pituitary gland, only tyrosine hydroxylase fibers, and not dopamine-β-hydroxylase immunoreactive fibers, were located throughout the neurohypophyseal tract and within the posterior pituitary in both pars intermedia and pars nervosa regions. Generally, the location and patterns of both catecholamine-synthesizing enzymes were similar to those reported for other mammalian species except for the absence of the A15 dorsal group and the very sparse dopamine-β-hydroxylase immunoreactive fibers and varicosities in the median eminence in the pig. These findings provide an initial framework for elucidating behavioral and neuroendocrine species differences with regard to catecholamine neurotransmitters. © 1996 Wiley-Liss, Inc.

Anterograde and retrograde mnemonic deficits after unilateral damage of neostriatal, ventral striatal and basal forebrain structures

Anterograde and retrograde mnemonic deficits after unilateral damage of neostriatal, ventral striatal and basal forebrain structures

Anterograde and Retrograde Mnemonic Deficits after Unilateral Damage of Neostriatal, Ventral Striatal and Basal Forebrain Structures

Anterograde and Retrograde Mnemonic Deficits after Unilateral Damage of Neostriatal, Ventral Striatal and Basal Forebrain Structures

Anterograde and retrograde mnemonic deficits after unilateral damage of neostriatal, ventral striatal and basal forebrain structures

Abstract A 51-year-old male patient (BL) was investigated three years after an intracerebral haemorrhage in the region of the left basal ganglia, resulting in unilateral damage of neostrlatum, ventral striatum, globus pallidus, and basal forebrain. BL manifested average Intelligence, somewhat sub-average attention and working memory, severe anterograde amnesia, and time-limited deficits in autobiographical memory (past decade) and Impaired recall of famous events (especially earller decades). The results are interpreted as supportive of a network of memory-associated regions in which the basal ganglia may take part. They are also considered to be lndicative of a hemispheric-specific recall of old episodic and semantic memories.

Development of acetylcholinesterase-positive thalamic and basal forebrain afferents to embryonic rat neocortex.

By combining anterograde and retrograde axonal tracing with AChE histochemistry, we demonstrate the sources of AChE-positive afferents to embryonic neocortex, the pathways they use, their time of arrival into cortex, and their initial invasion of the cortical plate. Acetylcholinesterase (AChE) is expressed by two populations of cortical afferents: AChE is permanently present in basal forebrain fibers and has been reported to be transiently localized in axons of the principal sensory thalamic nuclei over the first few postnatal weeks beginning at the middle of the first week. We first detect AChE-positive afferents histochemically in neocortex on embryonic day seventeen (E17) and determine that they arise from the principal sensory thalamic nuclei. AChE histochemistry labels the entire length of developing thalamocortical axons, including their growth cones and branches. These AChE-positive afferents enter the neocortex by the internal capsule and take an intracortical pathway centered on the subplate layer. As soon as these axons are detected, some have already begun to extend AChE-positive collateral branches superficially toward the cortical plate. By E19, a few collaterals have entered the deep part of the cortical plate and by E21 have densely invaded all but its most superficial undifferentiated part. AChE-positive afferents from basal forebrain structures reach the neocortex by three routes: the external capsule, the internal capsule, and the cingulate bundle. Among basal forebrain components, only the substantia innominata and nucleus basalis of Meynert reach the cortex by the internal capsule. Afferents from these two sources reach neocortex on E18, but are a very minor component of the total population of AChE-positive afferents at this age. Afferents from other basal forebrain components do not reach neocortex until several days later. The spatial and temporal patterns of AChE expression in developing thalamocortical axons indicate that it is useful for delineating their innervation of the primary sensory areas of embryonic neocortex, and suggest that AChE may function in axon extension and cortical differentiation.

Development of the age-related spontaneous spike-wave discharges in rat neocortex and exposure to a model neurotoxin.

In laboratory rats an epileptic-like spontaneous neocortical activity in the form of bursts of spike and wave discharges (SWD) develops gradually with age. High incidence of the SWD episodes is accompanied by other indices characteristic of advanced age: memory disturbances and atrophic changes within basal forebrain structures (Buzsaki et al. 1988b, Gage et al. 1988). Accordingly, it has been proposed that the number and duration of the SWD episodes be regarded as a diagnostic marker to distinguish between young and old brains (Buzsaki et al. 1988a). It is suspected that exposure to neurotoxins may accelerate the progress of age-related neurodegeneration by predisposing neurons to premature death and thus hasten the appearance of the age-related functional deficits (Weiss 1990). Analysing the development of SWD activity in exposed rats may be helpful for an assessment of the potency of the neurotoxin under study to exert such an effect. In the present work the influence of a three-month exposure to a model neurotoxin, ethanol (ETOH), on the development of the SWD activity in imp-DAK rats was investigated. It has been found that in rats given 10% ETOH solution as the only drink for three months, the incidence of the SWD episodes increased markedly. The increase was most clearly seen after ETOH withdrawal and on the 90th day after exposure no tendency to decline could be observed. The obtained data indicate that exposure to exogenous substances may exert a distinguishable long-lasting influence on the development of the SWD activity.

Brain corticotropin-releasing factor mediates ‘anxiety-like’ behavior induced by cocaine withdrawal in rats

Anxiety is a key symptom of the cocaine withdrawal syndrome in human addicts, and it is considered to be one of the major factors in precipitating relapse to chronic cocaine abuse. Corticotropin-releasing factor (CRF) plays an important role in the pathophysiology of anxiety and depression, and it may also be involved in the acute behavioral and neuroendocrine actions of cocaine. The role of endogenous CRF in cocaine withdrawal-induced anxiety was investigated in the present study. Animals were subjected to chronic cocaine (20 mg/kg, intraperitoneally, once a day for 14 days) administration. Rats tested 30 min after the last cocaine injection did not show withdrawal anxiety on the elevated plus maze or any alterations in brain CRF levels. Withdrawal (48 h) from chronic cocaine administration produced an intense anxiety-like behavior characterized by decreased open arm exploration. Immunoreactive CRF (CRF-LI) levels were selectively altered in the hypothalamus, in the amygdala and in the basal forebrain structures at the time of the behavioral anxiety, reflecting an increased activity of brain CRF systems. Daily intracerebroventricular (i.c.v.) pretreatment with an immunoserum raised against CRF completely prevented the development of anxiety induced by cocaine withdrawal. These data suggest that extrahypothalamic-limbic CRF hypersecretion may be involved in the development of anxiety related to cocaine withdrawal and that the CRF system may be a useful target for new pharmacotherapies for cocaine withdrawal and relapse.

Preoperative shunts in suprasellar tumours.

A series of 22 cases of large suprasellar tumours was studied retrospectively. These patients had undergone a preoperative shunt to facilitate surgical exposure of the tumour and to reduce intracranial pressure in critically ill patients. Our observations on the clinical progress of these patients following the shunt is analysed. Nine patients worsened to a varying degree following insertion of the shunt. Seven patients became drowsy, one developed worsening of vision and a hemiparesis, and one became an akinetic mute. The worsening was probably related to alteration of intracranial pressure dynamics and resultant compression in the hypothalamic region by subtle superior migration of the tumour. Operative difficulties were encountered during the dissection of the tumour from the neural structures in these cases. We conclude that with the availability of modern decongestive measures and basal surgical exposures, preoperative shunting is rarely indicated and can be occasionally dangerous. In the absence of actual proof, it is postulated that the secondary ventricular enlargement appears to be a protective mechanism of the brain helping to reduce tumour pressure on the basal forebrain structures.

Relationship of thalamic basal forebrain projection neurons to the peptidergic innervation of the midline thalamus.

To better understand the input-output organization of the midline thalamus, we compared the distribution of its peptidergic and monoaminergic afferents, which were visualized by using immunocytochemistry, with the distribution of neurons projecting to different basal forebrain structures, which were mapped using retrograde fluorescent tracers. Serotonin and most of the peptides were found throughout paraventricular thalamic nucleus (PV) and in other midline and intralaminar nuclei (type 1 pattern). Neuropeptide Y, alpha MSH and the catecholamine synthetic enzymes were largely restricted to dorsolateral PV (type 2 pattern). Vasopressin was found in dorsomedial PV and intermediodorsal nucleus in a pattern complementary to the type 2 distribution (type 3 pattern). Neurons projecting to accumbens core were present in paraventricular, intermediodorsal, and other midline nuclei. Neurons projecting to accumbens shell and to central amygdaloid nucleus were found in dorsal PV. The peptidergic zones were only loosely correlated with the distribution of different classes of projection neurons. The type 2 pattern overlapped best with neurons projecting to accumbens shell, and to a lesser extent to central amygdaloid nucleus, while the type 3 pattern overlapped best with neurons projecting to core of accumbens. This partial overlap suggests that some brainstem and hypothalamic nuclei preferentially affect different basal forebrain targets through the midline thalamus, and may allow, for example, information about stress to specifically influence accumbens shell and central amygdaloid nucleus. Nevertheless, most of the peptidergic afferents (type 1 pattern) to midline thalamus cover neurons projecting throughout the basal forebrain, which suggests that all of these neurons receive a variety of brainstem and hypothalamic inputs.

Localization of atrophy-prone areas in the aging mouse brain: Comparison between the brain atrophy model SAM-P/10 and the normal control SAM-R/1

Mouse inbred strain “SAM-P/10” (Senescence Accelerated Mouse) is a model of age-related brain atrophy. In this strain there is an earlier and more severe age-related deterioration in the conditional avoidance learning than the normal control inbred SAM-R/1 strain. The present study analysed age-related changes in brain area size using a computerized morphometric method. The region most vulnerable to age-related atrophy in SAM-P/10 was the frontal region of the cerebral cortex, including the prefrontal cortex. Other neocortical regions underwent diffuse atrophy. Posterior piriform cortex, entorhinal cortex, anterior olfactory nucleus, amygdala, caudate-putamen, nucleus accumbens and cerebellar cortex were atrophy-prone regions. The septum also underwent atrophy but other basal forebrain structures were intact. The hippocampus, diencephalon and brainstem structures showed no atrophie change. White matter structures did not change in size with aging except for the forceps minor of the corpus callosum, which showed age-related atrophy. On the contrary, SAM-R/1 showed a significant age-related atrophy only in a restricted part of the cerebral cortex, mainly in the parietal region. Other cortical regions, subcortical structures, diencephalon, brainstem structures, cerebellum and white matter were atrophy-resistant in SAM-R/1. The prefrontal cortex, entorhinal cortex, piriform cortex and striatum are closely interconnected and also connect with the amygdala which plays a key role in conditioning in the rodent. Age-related atrophy in all these structures in SAM-P/10 presumably accounts for the age-related deficits in conditional avoidance learning in this strain of mouse. Comparison between SAM-P/10 and SAM-R/1 or other well-known rodents indicates that SAM-P/10 is a unique rodent that spontaneously and rapidly develops progressive generalized cerebral atrophy, which is considered to be a pathological process rather than an accelerated aging process.

The effects of lesions of the entorhinal cortex and the horizontal nucleus of the diagonal band of broca upon performance of a spatial location recognition task

The effects of lesions of the horizontal nucleus of the diagonal band of Broca (HNDB) and the entorhinal cortex (ENTO) upon performance of a spatial location recognition task were assessed. Two hypotheses of entorhinal cortex function were considered in interpretation of the data. The first hypothesis assumes that the anatomical proximity and interconnections between the hippocampus and the entorhinal cortex are indicative of a functional similarity. The second hypothesis recognizes the interconnections of the hippocampus and the entorhinal cortex, but posits that the two structures have distinct functions. The hippocampus receives input primarily from the medial septum (MS), whereas the entorhinal cortex receives input from the HNDB and the MS. The study attempted to assess the function of the ENTO and the HNDB in a spatial location recognition task with the intent of comparing the findings to previous research of the hippocampus and MS. Performance of animals with HNDB lesions and the ENTO lesions was at chance levels for all serial positions. Results indicated that there are functional differences between the HNDB and other basal forebrain structures. Further, the performance deficit of the ENTO group does not differ from that observed following lesions of the hippocampus.

Structures mediating cholinergic reticular facilitation of cortical responses in the cat: effects of lesions in immunocytochemically characterized projections.

Cholinergic afferents to the neocortex controlled by the mesencephalic reticular formation (MRF) are known to transiently facilitate cortical excitability. In an attempt to identify the pathway mediating this effect in the cat visual cortex we combined retrograde tracing techniques with immunocytochemical methods to visualize the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT). In addition we examined, in acute electrophysiological experiments, whether local neurotoxin injections into nuclei of the basal forebrain interfered with the reticular facilitation of cortical evoked potentials. Cholinergic projections to area 17 originate from different centers in the homolateral substantia innominata/internal capsule, the septal nuclei, and the nuclei of the diagonal band of Broca. No direct cholinergic projection from the MRF to the visual cortex was observed. Retrogradely labelled cells intermingled with ChAT-positive neurons in the brainstem generally revealed immunopositivity for catecholaminergic markers. Local injections of neurotoxins in the substantia innominata blocked reticular facilitation, whereas local lesions of the septal nuclei and the nuclei of the diagonal band had no effect on MRF-induced facilitation. The blockage of the reticular facilitation of cortical evoked responses after unilateral lesions of the substantia innominata was bilateral, suggesting a cooperative interaction between basal forebrain structures of the two hemispheres. The anatomical and physiological data are discussed with respect to possible mechanisms of transient brainstem influences on cortical excitability.

Alterations of corticotropin-releasing factor-like immunoreactivity in different brain regions after acute cocaine administration in rats

Corticotropin-releasing factor (CRF) may mediate some of the neuroendocrine and behavioral responses to cocaine. In this study, the distribution of CRF-like immunoreactivity (CRF-LI) was determined in the hypothalamus and in several extrahypothalamic brain regions after acute cocaine administration in handled rats. CRF-LI decreased dose-dependently with cocaine administration in the hypothalamus and in the basal-forebrain structures. A small dose of cocaine (7.5 mg/kg) decreased CRF-LI in the hippocampus and in the frontal cortex. A significant, selective, dose-dependent increase in CRF-LI was found in the amygdala after cocaine injection. None of the investigated doses of cocaine altered CRF-LI in the striatum. These results suggest that acute cocaine administration alters brain CRF systems to contribute behavioral and neuroendocrine responses to cocaine.

Effects of cocaine on the contents of neurohypophyseal hormones in the plasma and in different brain structures in rats

The effects of acute and chronic cocaine treatments on the levels of the neurohypophyseal hormones oxytocin (OXT) and vasopressin (AVP) in the plasma and in different brain structures in rats were measured by radioimmunoassay (RIA). Acute cocaine treatment had no effect on the level of OXT in the plasma or in the amygdala, but increased OXT contents were measured in the hypothalamus and in the hippocampus. The OXT levels in the basal forebrain structures (including the septum and the nucleus accumbens) were decreased by a single dose of cocaine. The acute injection of cocaine increased the level of AVP in the plasma, and decreased contents of OXT were measured in the amygdala and in the basal forebrain. Repeated treatment with cocaine decreased the level of OXT in the plasma, hypothalamus and hippocampus. The AVP contents were decreased in all of the brain structures investigated, but no change was caused in the plasma level of AVP by repeated injections of cocaine. These results demonstrate complex, region-specific interactions between cocaine and the neurohypophyseal hormones in the brain and in the periphery underlying the alteration in behavioral and autonomic functions caused by acute and chronic cocaine exposure.