Effects of intracerebroventricular bombesin administration on local cerebral glucose utilization in the restrained and unrestrained rat

Intracerebroventricular (ICV) administration of bombesin (BN) induces a syndrome characterized by stereotypic locomotion and grooming, hyperactivity and sleep elimination, hyperglycemia and hypothermia, hyperhemodynamics, feeding inhibition, and gastrointestinal function changes. Mammalian BN-like peptides (MBNs), e.g. gastrin-releasing peptide (GRP), Neuromedin C (NMC), and Neuromedin B (NMB), have been detected in the central nervous system. Radio-labeled BN binds to specific sites in discrete cerebral regions. Two specific BN receptor subtypes (GRP receptor and NMB receptor) have been identified in numerous brain regions. The quantitative 2-[14C]deoxyglucose ([14C]20G) autoradiographic method was used to map local cerebral glucose utilization (LCGU) in the rat brain following ICV injection of BN (vehicle, BN O.1Jlg, O.5Jlg). At each dose, experiments were conducted in freely moving or restrained conditions to determine whether alterations in cerebral function were the result of BN central administration, or were the result of BN-induced motor stereotypy. The anteroventral thalamic nucleus (AV) (p=O.029), especially its ventrolateral portion (AVVL) (pcerebral metabolism within parts of the anterior thalamus, which is the principle relay in the limbic circuitry. BN effects were also observed in IGr, Mi, SCh, and ME. Effects of restraint were found in LOVL, LOOM, and LG. It is suggested that increased LCGU in AV and AVVL may be the result of functional change in the limbic circuitry and the hypothalamus caused by BN receptor functional modification. In IGr, increased LCGU following BN administration is considered to be mainly the result the activation of NMB receptor, a subtype of BN receptors. In SCh, increased LCGU is believed to be caused both by BN effects on the thalamic, the hypothalamic, and the limbic functions and by activation of GRP receptor, another BN receptors subtype found in SCh. In ME, increased LCGU is suggested to be caused by BN effects on the hypothalamic functions, especially those related to the neuroendocrine functions. None of the alterations seen in these regions reflects the emission of stereotyped motor behaviors. Rather, they reflect a direct influence of BN central administration upon functioning of the cerebral regions influenced by BN administration. The restraint effects seen in LO, including LOOM and LOVL, are suggested to be the result of altered behavioral expression. The restraint effects seen in LG is suggested to be the result of reduced locomotion.

Effects of Cerebral Blood Flow and PETCO2 on Cognitive Function During Passive Heat Stress

This thesis tested whether cognitive performance during passive heat stress may be affected by changes in cerebrovascular variables as opposed to strictly thermally-induced changes. A pharmacological reduction in cerebral blood flow (CBF) using indomethacin along with a hypocapnia-induced CBF reduction during passive heat stress (Tre ~1.5°C above baseline) were used to investigate any cerebrovascular-mediated changes in cognitive performance. Repeated measures analysis of variance indicated that One-Touch Stockings of Cambridge (OTS) performance was not affected by a significant reduction in CBF during passive heat stress. More specifically, OTS accuracy measures did not change as a result of either a reduction in CBF or increasing passive heat stress. However, it was found that OTS response time indices improved with increasing passive heat stress independent of CBF changes. In conclusion, a significant reduction in CBF does not cause additional changes in performance of an executive functioning task during severe passive heat stress.