Enhanced behavioral stereotypies elicited by intrastriatal injection D1 and D2 dopamine agonists in intact rats

Five components of behavior elicited by dopamine (DA) agonists (locomotor hyperactivity, sniffing, oral activity, grooming and paw nibbling) were evaluated after bilateral infusion of the selective D1 agonist fenoldopam (SKF 82526; 2.5-10 micrograms), the selective D2 agonist quinpirole (LY 171555; 5-40 micrograms) and the muscarinic cholinergic antagonist scopolamine (5-20 micrograms) into the ventral striatum of awake, unrestrained rats. Simultaneous bilateral infusion of various dose combinations of fenoldopam (2.5-10 micrograms) and quinpirole (5-20 micrograms) elicited dramatic increases in stereotyped behaviors relative to the effects produced by corresponding doses of each drug alone. Stereotyped sniffing and paw nibbling (self-directed oral activity) were markedly enhanced, whereas conventional oral behaviors (licking, chewing and/or biting) were either slightly or not at all increased. These potentiated responses were reduced or blocked by concomitant infusion of either the selective D1 antagonist SCH 23390 (1 and 5 micrograms) or the selective D2 antagonist sulpiride (0.15 microgram). Scopolamine (10 micrograms) only slightly increased the effects of quinpirole (5 micrograms) on both sniffing and oral behaviors, whereas it dramatically potentiated the effects of fenoldopam (2.5 micrograms) on oral activity; sniffing was only slightly increased. The effects of both drug combinations were almost completely antagonized by infusion of either SCH 23390 (1 microgram) or sulpiride (0.1 microgram). The results demonstrate that the synergistic effects of co-activation of D1 and D2 receptors observed after systemic administration are mediated at least in part by an interaction at the level of the striatum. Differences and similarities between the behaviors expressed after various treatments are discussed.     

Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.     

Enhanced take of spontaneous murine tumors in mice treated with inhibitors of macrophage and/or NK cell function

Both macrophages and NK cells have been suggested to play a role in recognizing and eliminating early, in situ neoplasms. Therefore we studied the effect of inhibitors of macrophage and/or NK cell function on the take of transplantable spontaneous murine tumors in syngeneic mice. The treatment of animals with trypan blue, a selective inhibitor of macrophage function, decreased considerably the period of latency of BSP3 adenocarcinoma; however, it did not increase the take of SP4, SP82 and SP84 adenocarcinomas. The treatment of recipients with neutral red, a selective inhibitor of NK cell function, enhanced the take of SP4 adenocarcinoma. The treatment of mice with agents depressing both macrophage and NK cell function (silica or carrageenan) decreased the both macrophage and NK cell function (silica or carrageenan) decreased the period of latency and/or increased the take of SP4, SP82 and SP84 adenocarcinomas. Carrageenan or a combined treatment with both trypan blue and neutral red also enhanced the take of BaF1, a benzo(a)pyrene-induced fibrosarcoma. We concluded that both macrophages and NK cells may function as effector cells of an antitumoral surveillance system.     

Morphological findings during retinal development and maturation in hereditary rod-cone degeneration in Abyssinian cats

The sequence of structural changes involved in postnatal photoreceptor differentiation, maturation and early degeneration was studied in young Abyssinian cats and kittens with hereditary rod-cone degeneration and compared to maturation in normal controls. In affected cats the earliest change seen was disorientation of outer segment discs in the majority of the rods, while other rods appeared to develop and mature normally. Such disorientation of discs (at oblique angles or parallel to the longitudinal axis of the outer segment, or whorls of discs) is considered as 'immaturity', since controls also showed a substantial number of disoriented rod outer segment discs at this young age. At postnatal day 35 the difference between affected animals and controls was marked with a high frequency of immature appearing rod outer segment discs in affected animals, while all rod outer segment discs were adult-like and arranged in an orderly manner in controls. Cones seemed unaffected at this age. More severe changes in affected rod outer segments in the form of disintegration of discs (vacuolization and clumping of disc material, or formation of debris), which we consider to represent degeneration, were first observed at the time when retinal maturation normally occurs in the cat, i.e. 150 days postnatally. Subsequently a drop-out of rods was seen, primarily of rods with disoriented and disintegrated outer segment discs, followed by a slow, progressive degeneration of rods that had developed and matured normally. Cones appeared normal during the time of retinal development and maturation and it was not until the age of 2-3 years (Narfstr?m and Nilsson, 1986, Incest. Ophthalmol, Vis. Sci. 27, 1569-76) that degenerative changes were seen also in cones.     

Optic nerve glioma and the management of optic nerve tumours in the young.

Thirty-one patients presenting as orbital optic nerve glioma have been reviewed with maximum follow-up of 14 years. Sixteen of these patients have been reported on previously and further follow-up is provided. Sixteen patients had a stable clinical course with little change over a period of up to 13.5 years. Neurofibromatosis was relatively common in this group (11/16). Fifteen patients had progressive enlargement of the tumour; the incidence of neurofibromatosis in this group was low (4/15). Eleven of these patients were explored neurosurgically and the optic nerve totally excised in 10 of them. The proximal cut end was normal in six patients and the chiasm has apparently remained free of tumour in all of them. We suggest a method of management of primary optic nerve tumours, both meningiomas and gliomas, in young patients.     

Nuclease hypersensitivity of the rat cytochrome P450IA1 gene

The bovine pancreatic deoxyribonuclease I (DNAase I) hypersensitivity of the rat cytochrome P450IA1 gene was investigated. A nuclease-hypersensitive region was observed at approximately 3.2 to 5.1 kilobase pairs upstream of exon 1 in adult and fetal rat liver. This region did not necessarily correlate with gene expression following 3-methylcholanthrene induction, although it may determine the potential for inducibility of this gene.