Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 112-132).

Behavioral responses to social odors in Syrian hamsters are regulated by brain structures including the medial amygdala (Me) and bed nucleus of the stria terminalis (BNST). The role of these areas in regulating social behaviors has been previously studied in detail. However, the chemical phenotypes of neurons in these areas have not been well defined. Based on previous literature, we hypothesize that there is an increase in Me GABAergic signaling in response to social odors in male hamsters. To test this, we quantified colocalization of Calbindin and Fos in the Me of male hamsters after odor exposure. There were no significant differences in the percentage of Fos+ cells that were CB+ between odor conditions, but the percentage of CB+ cells that were Fos+ was higher in subjects exposed to conspecific odors versus clean odors. This implies that CB+ neurons transmit social information in the Me of male hamsters.

Females are disproportionately affected by stress- related mood disorders. Child abuse is the single greatest environmental risk factor for mood disorders. An animal model of child abuse, juvenile social subjugation (JSS), was used to determine whether males and females differentially process stress, specifically in the bed nucleus of the stria terminalis (BST). Rats (n=36) were randomly assigned to one of three conditions: JSS, Benign Control (BC) or Handled Control (HC). Following this procedure, brains were processed for Fos, which indicates neural activity. It was hypothesized that the JSS condition would evoke more neural activation than other conditions and would do so more in females. Across both sexes, we hypothesized there would be significantly more activation in the posterior BST than in the anterior BST. Based on earlier research, we hypothesized there would be and a sex difference in total neuron number, favoring males, in the posterior BST.

Doctor of Philosophy (PhD) / The investigation into the relationship between neural plasticity in the rat forebrain associated with opiate-induced behaviours yielded two major results. The major finding of the functional neuroanatomy of acute morphine dependence was that doses of naloxone that induced hyperalgesia following a brief exposure to morphine, in previously drug-naïve rats, caused a specific induction of the inducible transcription factor (itf) proteins c-Fos and zif268 in the extended amygdala. Moreover, doses of naloxone that caused a simple reversal in morphine analgesia failed to induce itf proteins in these same brain regions. This increase in itf proteins was specific to regions of the extended amygdala that receive and process nociceptive information relayed via the spino-parabrachio-amygdaloid pathway and was not observed in other regions that are involved in supraspinal pain modulation such as the rostral ventromedial medulla and the periaqueductal gray. We also found that acute morphine increased c-Fos protein in the basolateral amygdala and the major output nucleus of the central amygdala the medial subdivision. Acute morphine also up-regulated c-Fos protein in striatal, midbrain, and hypothalamic nuclei. A unique finding of the current study was that prolonged exposure to morphine was required to induce c-Fos in these brain regions, as the subsequent administration of naloxone 30-minutes after morphine either reversed or blocked this induction. These results indicate the potential role of the amygdala in analgesia following systemic morphine and in pain facilitation during acute morphine abstinence. Investigation into the neurons and circuitry that undergo long-term neuroplasticity in response to repeated morphine exposure revealed that network-level changes in the distribution of Fos protein in the nucleus accumbens and striatum predicted both tolerance to catalepsy and psychomotor sensitisation. Drug-naïve rats became profoundly cataleptic following morphine, an effect that rats with a drug-history became tolerant. Rats with a history of morphine exposure showed an increase in stereotyped behaviours compared to drug-naïve rats. The major finding of this study was that a shift in the induction of c-Fos protein from a matrix predominance in drug-naïve rats toward a patch predominance in drug-sensitised rats in the accumbens core predicted both tolerance to catalepsy and sensitisation of oral stereotyped behaviours. Acute injection of morphine in a drug-naïve rat induced catalepsy and increased the number of c-Fos-positive neurons in matrix striatopallidal projection neurons of the rostral accumbens core. An increase in activity of striatopallidal projection neurons, which give rise to the indirect pathway, could potentially increase inhibitory drive to the pedunculopontine nucleus (PPN). The PPN, long known as a site of termination for basal ganglia output, is thought to direct the outflow of incentive-motivational and sensorimotor information from the nucleus accumbens to pons, medullary, and spinal cord nuclei translating the incentive impact of the stimuli into appropriate motor, autonomic and emotive responses (Winn et al., 1997). Inhibition of this nucleus would cause the animal to be unable to initiate a movement and in effect lock up, which is precisely what cataleptic postures look like. In contrast c-Fos-positive neurons were decreased in the rostral matrix and increased in patch striatonigral projection neurons along the rostro-caudal extent of the accumbens core when morphine was administered to drug-sensitised rats. Striatonigral neurons located in the patch give rise to the direct pathway innervating the dopaminergic neurons in both substantia pars compacta and the dopamine rich islands in the substantia nigra pars reticulata (Berendse et al., 1992; Gerfen, 1992; Furuta et al., 2002). Activity of this pathway is thought to be involved in the initiation of movement (Gerfen, 1992; Gerfen and Wilson, 1996), however, when this pathway is overstimulated as is the case when morphine is injected in drug-sensitised rats this could potentially cause increased activity of PPN neurons leading to repetitive psychomotor behaviours or stereotypy. This data adds to the growing body of evidence that suggests that long-term neuroadaptations induced by drugs of abuse including morphine that lead to behavioural sensitisation involves the circuitry that includes the nucleus accumbens.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 108-123). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 108-123). Also available on the Internet.

Orientador: Antonio Celso Pezzato / Resumo: RESUMO. Para avaliar a inclusão de diferentes combinações e níveis de prebióticos em substituição aos antibióticos melhoradores de desempenho, dois experimentos foram delineados. No primeiro estudo, 1250 pintos de corte machos, linhagem ROSS AP95, foram casualmente distribuídos em 5 tratamentos, com 10 repetições cada, objetivando testar diferentes proporções de mananos com β-glucanos e frutoligossacarídeos com galactoligossacarídeos, combinados e incluídos em dietas de frangos de corte. Os tratamentos consistiram de: CP, dieta basal (DB) +AMD; DB+BUT: DB + Butirato de Cálcio; GM1⁄3+FG2⁄3: DB + GLUCANMOS (1/3 da mistura) : FOS:GOS (2/3 da mistura); GM1⁄2+FG1⁄2: DB + GLUCANMOS (1/2 da mistura) : FOS:GOS (1/2 da mistura); GM2⁄3+FG1⁄3: DB + GLUCAN MOS (2/3 da mistura) : FOS:GOS (1/3 da mistura). No segundo estudo, 1250 pintos de corte machos, linhagem ROSS AP95, foram casualmente distribuídos em 5 tratamentos, com 10 repetições cada, objetivando testar diferentes níveis de inclusão de GLUCANMOS (67% da mistura) associado a FOS:GOS (1:1). Os tratamentos consistiram de: CP, dieta basal (DB) +AMD; 0,1%; 0,2%; 0,3% e 0,4% de inclusão da mistura prebiótica. Foram avaliados o desempenho, peso relativo de órgãos, barreiras físicas e imunológicas dos segmentos do intestino delgado (integridade de vilosidades, células caliciformes e linfócitos intraepiteliais), histomorfometria de Bursa de Fabricius e contagem diferencial de leucócitos no sangue, ainda, foram quantificados os ácidos grax... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Orexin A and B, also known as hypocretin 1 and 2, are two recently isolated hypothalamic peptides. As orexin-containing neurons are strategically located in the lateral hypothalamus, which has long been suspected to play an important role in feeding behaviors, initial studies were focused on the involvement of orexins in positive food intake and energy metabolism. Recent studies implicate a more diverse biological role of orexins, which can be manifested at different level of the neuraxis. For example, canine narcolepsy, a disorder with close phenotypic similarity to human narcolepsy, is caused by a mutation of hypocretin receptor 2 gene. Results from our immunohistochemical and functional studies, which will be summarized here, suggest that the peptide acting on neurons in the rostral ventrolateral medulla augment sympathoexcitatory outflow to the spinal cord. This finding is discussed in the context of increased sympathetic activity frequently associated with obesity.

Antibody coated microprobes, inserted into the spinal cord at the L4-5 level, were used to detect whether endomorphin-2 (Endo2) was released from spinal dorsal horns in anesthetized rats in response to formalin injected into the hindpaw footpads. Saline injections were used as a control and substance P (SP) was measured to verify activation of nociceptive afferent fibers. SP but not Endo2 was released during pre-stimulation periods. Saline injections did not cause the release of either Endo2 or SP from the spinal cord. Formalin injections caused an increase in Fos expression as well as a release of SP, but not Endo2 from the ipsilateral side dorsal horn in L4-5. We conclude that Endo2 does not play a role in mediating the in vivo responses to acute inflammatory nociceptive signals at the spinal level in the anesthetized rat model.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18500号 / 医博第3920号 / 新制||医||1005(附属図書館) / 31386 / 京都大学大学院医学研究科医学専攻 / (主査)教授 福山 秀直, 教授 河野 憲二, 教授 宮本 享 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM