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S A Lorens

Publications and source records attributed to S A Lorens.

At least 19 recordsLinked to original sources
PubMed2000

Amyloid-beta injection in rat amygdala alters tau protein but not mRNA expression.

Previously we demonstrated local and distant changes in tau protein immunoreactivity reminiscent of those seen in Alzheimer's disease (AD) following a unilateral injection of amyloid-beta (Abeta)(25-35) into the rat amygdala. To explore the relevance of these findings to AD, we compared the effects of Abeta(1-42) to those of Abeta(25-35). Injections of both Abeta(1-42) and Abeta(25-35) into rat amygdala resulted in increased tau-2 immunolabeling in neurons. To determine whether these alterations were due to changes in the expression of tau, we measured tau protein expression by Western blotting and tau mRNA isoform expression by the reverse transcription-polymerase chain reaction in the amygdala, hippocampus, and cerebellum following a unilateral injection of Abeta(25-35) or vehicle into the amygdala. The levels of tau proteins were increased bilaterally in the amygdala of Abeta(25-35)- compared to vehicle-treated animals 8 and 16 days following treatment. The molecular weights of tau proteins were decreased in the Abeta(25-35)-treated (59-69 kDa) compared to the vehicle-treated (67-72 kDa) animals 8 days following treatment. There were no changes in tau mRNA expression in any brain region examined. In this model, just as in AD, there is an increase in tau protein levels without a change in tau mRNA expression, suggesting that Abeta peptides may influence tau protein stability in both the rat and the human brain.

Alternative Splicing↗
PubMed1999

Neurokinin-3 receptor distribution in rat and human brain: an immunohistochemical study.

Autoradiographic and immunohistochemical studies have shown that the neurokinin-3 receptor is widely distributed in the rodent CNS. Expression of the neurokinin-3 receptor in human brain, however, has been debated. These conflicting findings, as well as the poor resolution of autoradiographic images, prompted us to develop a polyclonal antibody against an oligopeptide derived from the carboxy-terminus consensus sequence of both the rat and human neurokinin-3 receptor ([C]ASTTSSFISSPYTSVDEYS, amino acids 434-452 of the rat neurokinin-3 receptor). Western blot analysis of both human and rat brain tissue revealed a major band in the molecular weight range 65,000-67,000, the proposed molecular weight of the neurokinin-3 receptor based on its amino acid sequence and presumed glycosylation state. The distribution of selective high affinity neurokinin-3 receptor agonist [3H]senktide binding and neurokinin-3 receptor immunoreactivity were virtually identical in the brains of male Fischer 344 rats. The highest concentrations of neurokinin-3 receptors were observed in cortical layers IV-V; the basolateral amygdaloid nucleus; the hypothalamic paraventricular, perifornical and supraoptic nuclei; the zona incerta; and the entopeduncular and interpeduncular nuclei. [3H]senktide binding and neurokinin-3 receptor immunoreactivity were compared in homologous cortical areas of the human and rat brain. In contrast to the rat, autoradiographic analysis of normal control human brains (35-75 years) revealed a distinct and predominant superficial cortical labeling in the glia limitans and the cortical layer I. However, neurokinin-3 receptor immunoreactivity could be found not only in the superficial cortical layers, but also on pyramidal neurons and astrocytes in the neuropil and white matter. These findings suggest species differences in both the cellular and anatomical distribution of the neurokinin-3 receptor.

Amino Acid Sequence↗
PubMed1998

Effect of d-fenfluramine on the lymphocyte response of HIV+ humans.

The objective of this study was to analyse the effect of d-dexfenfluramine (d-FEN) on the human lymphocyte response, in vitro. Experiments were designed to determine whether d-FEN augments specific human immune parameters associated with protection from opportunistic microbial pathogens and particularly focuses on d-FEN as a means by which to augment the function of CD8+ and CD4+ lymphocytes. Lymphocytes were examined for three reasons: (1) for their ability to inhibit the growth of Candida albicans; (2) for their ability to proliferate in response to a mitogen; and, (3) their cytokine profile (vis., production of IL-2, IFN-gamma and TNF-alpha). Peripheral blood mononuclear cells (PBMC) were obtained from 20 HIV+ patients. The patients were diagnosed as HIV+ within the past 0.5-9 years. d-FEN was found to augment the capacity of CD8+ lymphocytes to inhibit the growth of the opportunistic microbial pathogen, C. albicans. d-FEN enhanced the capacity of CD4+ lymphocytes to proliferate in response to the mitogen, Concanavalin A, and to increase the amount of IL-2 produced by CD4+ and CD8+ lymphocytes from AIDS patients. d-FEN increased the number of CD4+ and CD8+ lymphocytes that produced IFN-gamma from either non-AIDS or AIDS patients and increased the number of AIDS patient's CD8+ lymphocytes that produce TNF-alpha. These in vitro data suggest that d-FEN may be effective in enhancing immune function in immunocompromised individuals.

Adjuvants, Immunologic↗
PubMed1997

Androgen inhibits neurotransmitter turnover in the medial prefrontal cortex of the rat following exposure to a novel environment.

Previous studies have demonstrated that gonadal steroid hormones affect the neuroendocrine response to a novel environment and other stressors. Introduction to a novel environment also increases neurotransmitter turnover in the medial prefrontal cortex (MPFC). In this study, we examined the possibility that gonadal steroid hormones could similarly modulate the neurotransmitter response to a novel environment in the MPFC of the male rat. Male Fischer 344 rats at 3 months of age were gonadectomized (GDX'd) and implanted with Silastic capsules containing dihydrotestosterone propionate (DHTP, a non-aromatizable form of androgen), 17 beta-estradiol (E), or placebo. Control animals were left intact. Each of these groups was further divided into a group introduced to a novel environment or a home cage control group. Animals exposed to a novel environment were killed after spending 20 min in a novel open field, whereas control animals were killed immediately upon removal from their home cage. Using high performance liquid chromatography, the MPFC was assayed for tissue levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA); norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); or serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA). The introduction to a novel environment caused significant increases in turnover of all three neurochemicals examined as estimated by metabolite/precursor ratios. These increases were characterized by increases in DOPAC, HVA, MHPG and 5-HIAA coupled with decreases in DA, NE and 5-HT. There was no effect of GDX on neurotransmitter turnover, however, treatment of GDX animals with DHTP prevented the open field induced increase in DOPAC/DA, MHPG/NE, and 5-HIAA/5-HT ratio. Treatment of GDX animals with estrogen had the opposite effect of DHTP, DOPAC/DA and MHPG/NE ratios increased to a greater level following the introduction to a novel environment than in GDX or intact animals. Examination of behavior in the open field showed significant decreases in activity in the DHTP-treated group but not in any other behavioral parameter (rears, nose pokes). Since the non-aromatizable androgen, DHTP, is presumably acting via androgen receptors, and E is presumably acting via estrogen receptors, these data suggest that, in the MPFC of male rats, androgen and estrogen receptors act in an opposing fashion to modify neurotransmitter turnover. This suggests that local changes in the relative levels of androgen and estrogen can have profound effects on the neurobiological response of the medial prefrontal cortex to stimuli.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Laterality in the histological effects of injections of amyloid-beta 25-35 into the amygdala of young Fischer rats.

We have observed that single amyloid-beta 25-35 (A beta) injections (5.0 nmol) into the right amygdala of rats produce progressive cytoskeletal and astrogliotic reactions not only within the amygdala, but also in distal brain regions that project to the amygdala. To determine if these effects are potentiated by bilateral injections, we injected A beta (5.0 nmol) into the left and right amygdala of young male Fischer rats. Animals were sacrificed 32 days postoperatively. Bilateral infusions of A beta induced significant neuronal shrinkage, tau-2 neuronal staining, and reactive astrocytosis within the right amygdala and/or hippocampus, compared with vehicle-treated rats. Surprisingly, the same brain regions within the left hemisphere were significantly less affected even though no differences were observed between the left and right amygdala in the size of Congored-positive A beta deposits. Unilateral injections of A beta into the left amygdala led to significant histological changes in the right amygdala and hippocampus, but not in the same brain regions within the left hemisphere. These results suggest a laterality in the histopathological effects of A beta in male Fischer rats. Identification of the cause for the lateralized effect of A beta may prove valuable for understanding the etiology of Alzheimer disease and provide possible therapeutic strategies designed to slow the progression of the disease.

Amygdala↗
PubMed1996

Responses to novelty stress in female F344 rats: effects of age and d-fenfluramine treatment.

To elucidate some of the mechanisms underlying the neuroendocrine and neurochemical changes associated with age in female rats, we administered the serotonin (5-HT) releaser and reuptake inhibitor, d-fenfluramine (d-FEN; 0.0 or 0.6 mg/kg/day, PO) for 30-38 days to young (4 month) and old (21 month) F-344 female rats. Animals were placed into a novel open field (OF) for 20 min before sacrifice. Control animals were sacrificed immediately upon removal from their home cage (HC). Old rats exhibited significantly (p < 0.05) less exploratory behavior and a smaller CORT response to OF than young animals. d-FEN treatment had no effect on plasma ACTH and CORT levels or exploratory behavior. The old HC rats had significantly (p < 0.05) higher plasma levels of prolactin (PRL) than the young HC rats. A stress induced increase in PRL secretion was observed in the old rats only, which was attenuated by d-FEN treatment. In the OF groups, both the young and old rats showed elevated medial frontal cortex (MFC) dopamine turnover (DOPAC/DA ratio), but only the young rats exhibited an elevation in norepinephrine (NE) turnover (MHPG/NE ratio). d-FEN treatment blocked the stress-induced increase in NE turnover in the young rats and the increase in DA turnover in the old rats. These data suggest that 5-HT activity could be involved in the age-related changes in the MFC catecholamine and PRL responses to stress in female rats.

Adrenocorticotropic Hormone↗
PubMed1996

Effect of d-fenfluramine on the local immune response to the opportunistic microbial pathogen Candida albicans.

In this study the effects of systemic administration of d-fenfluramine on the local lymphocyte response to Candida albicans was evaluated. Experimental animals were challenged intradermally with Candida albicans and then administered d-fenfluramine (d-FEN 1 mg/kg per day, i.p.) or a balanced salts solution. At successive time intervals, lymphocytes were derived from the draining lymph nodes and from the dermal sites of active microbial challenge. A CD8+ lymphocytosis was observed in all animals challenged with Candida albicans. The CD8+ lymphocytosis was augmented in animals that received d-FEN. Phenotypically, lymph nodes from d-FEN treated animals showed a marked increase in CD3+ and CD8+ lymphocytes, a modest increase in the numbers of NK1.1+ cells and a decrease in Ig+ lymphocytes. Functionally, lymphocytes from the site of active microbial challenge were capable of direct growth inhibition of Candida albicans. The anti-fungal activity was augmented in the animals that received d-FEN. These results suggest that d-FEN augments the local T lymphocyte response to an important microbial pathogen by increasing the number of T lymphocytes draining the site of microbial infection and by increasing the biological activity of the lymphocytes at the site of the infection.

Animals↗
PubMed1996

Reduction of calcineurin enzymatic activity in Alzheimer's disease: correlation with neuropathologic changes.

Neurofibrillary tangles (NFT), neuritic plaques, and dystrophic neurites are the classic neuropathologic hallmarks of Alzheimer's disease (AD), all of which contain to varying degrees abnormally and/or hyperphosphorylated forms of the microtubule-associated protein tau. Protein phosphatase 2B (calcineurin) dephosphorylates tau isolated from AD brains to control levels in vitro as well as regulates tau phosphorylation and function in vivo. It has been hypothesized that the changes in tau phosphorylation observed in AD may be due to increases in kinase activity and/or decreases in phosphatase activity. In order to investigate the latter possibility, we examined calcineurin enzyme activity using the substrate para-nitrophenyl-phosphate (pNPP) in postmortem brain samples from individuals with moderate to severe AD (n = 8) and age-matched controls (n = 7). The stimulation of calcineurin activity by manganese chloride (1 mM) was reduced by 60% (p < 0.01) in whole-cell homogenates prepared from AD temporal cortex (Brodmann area 38). On the other hand, in P2 membrane fractions, the stimulation of calcineurin activity by manganese chloride as well as nickel chloride (1 mM) was reduced by 37% (p < 0.05) and 79% (p < 0.01), respectively. The manganese-stimulated calcineurin activity in the temporal cortex inversely correlated with both the number of NFT (r = -0.60, p < 0.02) and neuritic/core plaques (r = -0.63, p < 0.02) in whole-cell homogenates, but only with NFT (r = -0.61, p < 0.02) in P2 membrane fractions. The nickel-stimulated calcineurin activity did not correlate with neuropathology measures in either whole-cell or P2 membrane fractions. In striate visual cortex (Brodmann area 17), an area relatively unaffected in AD, neither whole-cell nor P2 membrane calcineurin activity were significantly altered. To our knowledge, this is the first report of a reduction in calcineurin phosphatase activity in AD which correlates with the neuropathological features in a region-, subcellular fraction-, and divalent cation-specific manner.

Aged↗
PubMed1995

beta-Amyloid 25-35 and/or quinolinic acid injections into the basal forebrain of young male Fischer-344 rats: behavioral, neurochemical and histological effects.

beta-Amyloid peptides have been shown to potentiate the neurotoxic effect of excitatory amino acids in vitro. In order to determine if this occurs in vivo, four experiments were performed. We injected beta-amyloid 25-35 (beta A 25-35) and/or quinolinic acid (QA) bilaterally into the ventral pallidum/substantia innominata (VP/SI) of rats. Control rats received vehicle infusions. A high dose of QA (75.0 nmol/3 microliters) increased open field activity and impaired spatial learning in the Morris water maze, but did not affect the acquisition of a one-way conditioned avoidance response. These changes were associated with histological evidence of neurotoxicity and a reduction in amygdaloid but not frontal cortical or hippocampal choline acetyltransferase (ChAT) activity. A lower dose of QA (37.5 nmol/3 microliters) produced no behavioral effects. It reduced amygdaloid ChAT activity to a lesser extent than the higher dose (15% vs. 29-37%), and caused less histological damage. beta A 25-35 (1.0 or 8.0 nmol/3 microliters) failed to produce behavioral, histological or neurochemical signs of toxicity. Neither dose of beta A 25-35 potentiated the effects of QA (37.5 nmol) on behavior or amygdaloid ChAT activity, and did not appear to increase the histological damage caused by QA. These results suggest that in vivo beta A 25-35 is not neurotoxic and does not potentiate the neurotoxicity of QA in the VP/SI. Further, the histological effects of a high dose of beta A 25-35 (8.0 nmol/3 microliters; a cavitation containing a Congo red positive proteinaceous material) are quite distinct from those produced by a high dose of QA (75.0 nmol/3 microliters; widespread neuronal loss and gliosis).

Amyloid beta-Peptides↗
PubMed1995

Within-subject decline in delayed-non-match-to-sample radial arm maze performance in aging Sprague-Dawley rats.

A within-subject design was used to examine delayed-non-match-to-sample radial arm maze performance in aging (6-18 months) male Sprague-Dawley rats. A decrease in correct choices and an increase in retroactive errors were observed at all retention intervals at 18 months of age compared with performance at 6 or 12 months. No age by retention interval interaction was observed. Neither age nor increasing retention interval influenced proactive errors during the retention test. The observation of an age- and delay-dependent increase in retroactive errors, but not proactive errors, suggests that the deficit relates to a memory dysfunction as opposed to a generalized performance deficit.

Aging↗
PubMed1994

Androgen regulation of adrenocorticotropin and corticosterone secretion in the male rat following novelty and foot shock stressors.

To examine mechanisms responsible for sex differences in hypothalamo-pituitary-adrenal (HPA) axis responsiveness to stress, we studied the role of androgens in the regulation of the adrenocorticotropin (ACTH) and corticosterone (CORT) responses to foot shock and novelty stressors in gonadectomized (GDX) or intact male F344 rats. Foot shock or exposure to a novel open field increased plasma ACTH and CORT, which was significantly greater in GDX vs. intacts. Testosterone (T) or dihydrotestosterone propionate (DHT) treatment of GDX animals returned poststress levels of ACTH and CORT to intact levels. Estrogen treatment of GDX males further increased poststress CORT secretion above GDX levels. There was no difference in the ACTH response of anterior pituitaries from intact, GDX, and GDX+DHT animals to CRF using an in vitro perifusion system. There were no differences in beta max or binding affinity of type I or II CORT receptors in the hypothalamus or hippocampus of intact, GDX, or GDX+DHT groups. These data demonstrate an effect of GDX on hormonal indices of stress. The increased response in GDX rats appears to be due to the release from androgen receptor mediated inhibition of the HPA axis. This inhibition by androgen is not due to changes in anterior pituitary sensitivity to CRH, nor to changes in type I or type II corticosteroid receptor concentrations.

Adrenocorticotropic Hormone↗
PubMed1994

Spatial learning deficits in the aged rat: neuroanatomical and neurochemical correlates.

To assess neurochemical and neuroanatomical correlates of age and spatial learning, aged Sprague-Dawley male rats (20-22 mo) were divided into two groups based on their ability to locate a hidden platform in a Morris water maze. An "old good" group of rats acquired the task as rapidly as young (3-6 mo) animals, whereas an "old poor" group of rats failed to show improvement on subsequent testing days. Age-related changes included (a) a significant decrease in the number of choline acetyltransferase (CHAT) immunoreactive cells in the ventral cell group of the septal complex (28%); (b) a decrease in caudate dopamine levels (-11%); and (c) an increase in 5-HIAA levels in the n. accumbens (+25%) and hippocampus (+18%). Spatial learning related changes in aged rats included: (a) an increase in medial frontal cortex 5-HIAA levels (52%) in the old good learners but not old poor learners with (b) a decrease in medial frontal cortex dopamine levels (-24%) only in the old poor learners group and (c) a decrease in n. accumbens DOPAC (-22%) and HVA (-23%) in the old good learners group only. The present study demonstrates age-related but not spatial learning related decrease in CHAT immunoreactive cells in the ventral cell group of the septal complex. Therefore, either the cholinergic cell loss in the septum is unrelated to the acquisition of spatial learning measured by the Morris water maze, or it is a permissive effect along with specific alterations in forebrain dopaminergic and serotonergic systems, particularly in the medial frontal cortex and n. accumbens. The above findings are consistent with findings seen in Alzheimer's disease where both basal forebrain cholinergic nuclei and cortical projecting brainstem monoamine systems are affected.

Aging↗
PubMed1994

AF64A affects septal choline acetyltransferase but not parvalbumin immunoreactive cells.

Rats received bilateral intracerebroventricular (ICV) infusions of either AF64A (1.5 nmol/ventricle; n = 9) or vehicle (3.0 microliters/ventricle; n = 7). Four weeks later, the animals were anesthetized and their brains processed to visualize and quantify choline acetyltransferase (ChAT) immunoreactive (IR) and parvalbumin-IR GABAergic neurons in the septal complex by immunocytochemistry (PAP method). AF64A significantly reduced the number of ChAT-IR perikarya in the medial septum (28%), ventral limb of the diagonal band of Broca (30%), and horizontal limb of the diagonal band of Broca (20%), but did not affect the number of parvalbumin-containing GABAergic neurons in any of the septal subdivisions. These results provide further evidence that AF64A is a selective cholinotoxin.

Animals↗
PubMed1993

Neuroendocrine and neurochemical responses to novelty stress in young and old male F344 rats: effects of d-fenfluramine treatment.

To understand some of the mechanisms underlying the neuroendocrine and neurochemical changes associated with aging, we administered the serotonin [5-hydroxytryptamine (5-HT)] releaser and reuptake inhibitor d-fenfluramine (d-FEN; 0.0, 0.2, or 0.6 mg/kg/day, p.o) for 30-38 days to young (4 months) and old (22 months) F344 male rats. Rats were stressed by placement into a novel open field (OF) for 20 min before sacrifice. Control animals were sacrificed immediately upon removal from their home cage (HC). Old rats exhibited less (p < 0.05) exploratory behavior than young rats, which was not altered by treatment with d-FEN. Old HC rats also had higher (p < 0.05) basal plasma levels of adrenocorticotropic hormone (ACTH) and prolactin (PRL) than young HC rats. Old OF rats showed higher (p < 0.05) levels of ACTH and corticosterone (CORT) than young OF animals. A stress-induced increase in PRL secretion was not observed in old rats. Subchronic low-dose d-FEN normalized the enhanced ACTH and CORT responses of old animals to novelty. In addition to these endocrine changes, stress-induced increases in medial frontal cortex (MFC) dopamine (DA) and norepinephrine (NE) turnover also were observed. The increase in NE turnover was greater (p < 0.01) in old than in young rats. d-FEN treatment blocked the stress-induced increase in MFC NE but not MFC DA turnover in both young and old rats. These data support a role for 5-HT and/or NE in some age-related neuroendocrine perturbations and suggest that increased 5-HT neurotransmission can normalize the hyperactivation of the hypothalamo-pituitary-adrenal axis of old male rats.

Adrenocorticotropic Hormone↗
PubMed1992

Preliminary evidence for methamphetamine-induced behavioral and ocular effects in rat offspring following exposure during early organogenesis.

Gravid Sprague-Dawley CD (VAF) rats received 50 mg/kg (d,l)-methamphetamine (MA) HCl (expressed as free base, N = 15) or distilled water (N = 6) by SC injection x 2/day in a 3 ml/kg volume on embryonic (E) days 7-12. Control rats were pair-fed to MA-exposed dams on days E7-18. No control dams failed to deliver; however, of 15 MA-exposed dams 4 did not deliver (2 died and 2 had completely resorbed litters). One additional MA litter had all the offspring die shortly after birth. There was no difference between groups on offspring postnatal (P) body weight. The offspring exposed prenatally to MA had significantly lower olfactory orientation scores (P9, 11, 13) to their home cage scent. In a test of early activity (P10, 12, 14) the MA-exposed progeny were marginally less active than controls. MA-exposed offspring exhibited hyperreactivity and marginally shortened response latency on a test of acoustic startle (P27). Motor activity showed no differential response in MA treated or control offspring to MA (P63) or fluoxetine challenge (P70). However, the MA offspring were more active than controls with respect to central and side activity during the second week of testing. No group differences were found for performance in a straight swimming channel or on the number of errors committed or latency to escape in a complex (Cincinnati) water maze (P84). Prenatal exposure to MA also induced eye defects (i.e., anophthalmia, microphthalmia and folded retina) in 16.7% of the progeny. However, MA did not effect hippocampal or neostriatal monoamine levels when measured on P28.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Muscimol injections into the median raphe nucleus increase serum ACTH and corticosterone concentrations via a nonserotonergic mechanism.

Midbrain raphe serotonin (5-HT) neurons can influence the pituitary-adrenal axis. The midbrain raphe nuclei also contain a number of non-5-HT neurons, including gamma-aminobutyric acid (GABA) interneurons which can modulate 5-HT neuronal activity. We investigated the effects of intraraphe injections of the GABAA agonist, muscimol, on serum adrenocorticotropin hormone (ACTH) and corticosterone concentrations. Rats were infused with muscimol (0, 25, 50, and 100 ng in 0.5 microliters saline) into the median raphe nucleus (MR). The animals were killed 30 min later, and trunk blood was collected for measurement of serum concentrations of ACTH and corticosterone by radioimmunoassay. Muscimol dose dependently increased plasma concentrations of these two pituitary-adrenal hormones. In order to determine the role of MR 5-HT neurons in these effects, separate groups of implanted animals were infused with either the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) or ascorbic acid vehicle into the MR. Two weeks later, the animals were infused with muscimol (100 ng in 0.5 microliters) and sacrificed as above. Treatment with 5,7-DHT, which markedly reduced hippocampal concentrations of 5-HT (-83%) and 5-HIAA (-73%), did not block intra-MR muscimol-induced elevations in ACTH and corticosterone. Thus, 5-HT neurons within the MR apparently do not mediate the increased activity of the pituitary-adrenal axis produced by stimulation of MR GABAA receptors.

5,7-Dihydroxytryptamine↗
PubMed1991

Intra-midbrain raphe injections of the neurokinin-3 agonist senktide inhibit food and water intake in the rat.

Microinjection and lesion studies have implicated the midbrain dorsal (DR) and median raphe (MR) nuclei in behavioral arousal. This behavioral state is manifested as locomotor hyperactivity, hyperphagia, hyperdipsia and increases in plasma corticosteroid release. Intra-midbrain raphe injections of the GABAA agonist muscimol elicit this behavioral activation. We have demonstrated that similar infusions of tachykinins produce locomotor hyperactivity through activation of neurokinin-3 (NK-3) receptors located on serotonin cell bodies. The purpose of the present study was to determine the effects of intra-MR and DR infusions of senktide, an NK-3 agonist, on food and water consumption in nondeprived rats. Male Sprague-Dawley rats were implanted with indwelling intra-MR or intra-DR cannula. Infusions of muscimol (25 ng/0.5 microliters) into the MR increased water intake, while MR and DR infusions increased food consumption. In contrast, intra-MR injections of senktide decreased water intake and intra-MR and DR injections decreased food intake. The results suggest that the behavioral states induced by muscimol and neurokinin infusions into the raphe are distinct and that raphe/neurokinin pathways are involved in consummatory mechanisms.

Animals↗