Search PubMed⌕ Search

Biomedical subjects

B J Hoffer

Publications and source records attributed to B J Hoffer.

At least 109 records · Page 6Linked to original sources
PubMed1988

Toluene exposure during maturation of intraocular brain tissue transplants: alterations of host and graft cerebellar Purkinje neuron function and sensitivity to norepinephrine.

The effects of chronic toluene exposure on central neurons were examined using syngeneic grafts into the anterior chamber of the eye. Young adult albino rats with intraocular brain transplants inhaled toluene (1000 ppm) for 9 weeks starting at the time of transplantation, or from Week 8 to 17 after the graft was placed in oculo. Control animals were exposed to room air during the same intervals. Toluene treatment during development did not affect general growth or morphology of any of the brain areas examined. The distribution of neurofilament or glial fibrillary acidic protein immunoreactivity was similar in the experimental group and control group as well. Extracellular recordings of cerebellar Purkinje neurons showed a significantly reduced spontaneous firing rate, of 15-25%, both in intraocular transplants and in cerebellum in situ in toluene exposed animals. Postsynaptic sensitivity of intraocular and in situ Purkinje neurons to norepinephrine (NE) was evaluated. Purkinje neurons in transplants exposed to toluene during development were markedly supersensitive to superfused NE as compared to controls, while neither Purkinje neurons in mature cerebellar grafts nor cerebellum in situ showed any effects of the toluene treatment on NE sensitivity. The tissue content of NE in transplants exposed to toluene during maturation, evaluated with high-performance liquid chromatography coupled with electrochemical detection, was greater than that in the control grafts. Moreover, the content of free (3-methoxy-4-hydroxyphenyl) ethylene glycol (MHPG) was increased in both transplant and host cerebellum after toluene exposure. Taken together, these data indicate that toluene exposure during development of cerebellar grafts in oculo causes changes in postsynaptic noradrenergic sensitivity as well as decreased spontaneous activity of Purkinje neurons. Toluene exposure of adult cerebellum in situ or in oculo appears to decrease the Purkinje neuron discharge rate and increase NE turnover, but has no marked effect on postsynaptic NE sensitivity.

Administration, Inhalation↗
PubMed1988

Potentiation of morphine-elicited circling by dopaminergic uptake blockade.

Contraversive circling induced by unilateral infusions of morphine (7.5 nanomoles or 5 micrograms) into the ventral tegmental area was studied under conditions of dopamine uptake inhibition. Dopamine uptake blockade with either nomifensine (2.5 mg/kg) or GBR 13069 (2.0 mg/kg) resulted in a 3-fold increase in the rate of circling. Naloxone (1.5 mg/kg) attenuated but did not completely block the potentiated circling. These data are consistent with the hypothesis that morphine causes contraversive circling through local activation or disinhibition of dopaminergic cell firing.

Animals↗
PubMed1988

An improved calibration procedure for computer-based quantitative autoradiography utilizing a mathematical model for the non-linear response of camera and film.

A mathematical model which accounts for the non-linear response of both the camera and film in computer-aided quantitative autoradiography is derived. This model and the algorithm to fit the data for radioactive standards by a non-linear least-squares procedure to this model are described. The usefulness of this technique is demonstrated by employing it to analyze a set of 14C-labeled brain paste standards which were exposed to Ultrofilm in such a way that the full response range of the film was used. This technique can be readily implemented on most commercially available image analysis systems and is compatible with most types of video cameras.

Algorithms↗
PubMed1988

Effects of electrical stimulation of brain reward sites on release of dopamine in rat: an in vivo electrochemical study.

Behavioral studies suggest that mesencephalic dopamine neurons mediate the rewarding effects of electrical stimulation of the medial forebrain bundle. Yet there is little direct evidence that rewarding electrical stimulation actually activates dopamine-containing neurons. The purpose of the present study was to determine, using in vivo electrochemistry, if electrical stimulation applied to lateral hypothalamic or ventral tegmental reward sites would elicit changes in extracellular levels of dopamine. In vivo high speed chronoamperometric recordings were performed in anesthetized rats that had been previously trained to respond for rewarding electrical stimulation of the medial forebrain bundle or ventral tegmental area. We found that a single 500 msec train of pulses elicited a small transient electrochemical signal, the magnitude of which was dependent on the pulse duration and frequency. This signal was potentiated by inhibition of dopamine reuptake. Prolonged electrical activation with a self-stimulation-like regimen resulted in the gradual accumulation of an electroactive compound, tentatively identified as dihydroxyphenylacetic acid (DOPAC). Taken together, the data reported here support the idea that rewarding electrical stimulation causes the release of dopamine.

Animals↗
PubMed1987

Age-related changes in cerebellar noradrenergic pre- and postsynaptic mechanisms: intrinsic vs extrinsic determinants evaluated with brain grafts in oculo.

Intrinsic versus extrinsic determinants of changes in cerebellar noradrenergic transmission during senescence in the rat were measured using homologous cerebellar grafts in oculo. Postsynaptic sensitivity of Purkinje neurons to catecholamines was determined by perfusing the anterior eye chamber with known concentrations of norepinephrine (NE) dissolved in a balanced salt solution. NE elicited a dose-dependent slowing of spontaneous Purkinje neuron discharge in both young (3-6 months) and aged (20-22 months) cerebellar grafts. Hill plots demonstrated that the dose-response relationships in both age-groups were linear and parallel to one another. Aged transplant Purkinje neurons manifested a marked and highly significant subsensitivity to NE with an EC50 of 583 microM, as compared with an EC50 of only 15.9 microM in the young grafts. Young grafts in 15-21-month-old hosts manifested an EC50 of 20 microM for the depressant actions of NE. Collaterals of host iris sympathetic fibers innervate the grafts. Activity of these fibers can be reflexly altered by changing illumination of the retina. The dynamics of presynaptic NE release from these fibers was evaluated using in vivo electrochemistry with Nafion-coated graphite epoxy capillary electrodes, which are highly selective for the monoamine neurotransmitters. As illumination of the ipsilateral retina is increased, the release of catecholamine in the cerebellar graft decreases. A mean change in the extracellular electroactive species of 4.2 +/- 0.6 microM was found in young cerebellar grafts. Equivalent stimuli induced a mean change of 2.3 +/- 0.8 microM in aged grafts. However, this diminished release was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

The electrophysiological effects of nicotine in the rat cerebellum: evidence for direct postsynaptic actions.

The agonistic actions of nicotine in the cerebellum were dependent on the type of cerebellar neuron studied. Purkinje cells were inhibited and cerebellar interneurons were excited by pressure-ejected nicotine. The simultaneous iontophoresis of Mg2+ failed to block nicotine agonistic actions on either cell type. Since Mg2+ reduces presynaptic release of neurotransmitters, our findings suggest that the pharmacological actions of nicotine on cerebellar neurons are due to direct postsynaptic mechanisms.

Action Potentials↗
PubMed1987

In vivo electrochemical demonstration of potassium-evoked monoamine release from rat cerebellum.

In vivo electrochemical methods were employed to study the potassium (K+)-evoked release of monoamines from the cerebellum of the chloral hydrate anesthetized rat. K+-evoked releases were elicited using micropipette-Nafion-coated graphite epoxy electrode arrays in the granule/Purkinje cell layer, molecular layer, and white matter. These recorded releases were generally found to be reversible, moderately dose-dependent, and reproducible. However, the temporal dynamics of the releases were different for the cell layer versus molecular layer records. Releases were infrequently observed in cerebellar white matter, an area which is relatively devoid of monoamine containing terminals. The signals recorded from the cell and molecular layers were significantly attenuated by pretreatment with the selective noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). Local pretreatment with nomifensine, a potent catecholamine reuptake blocker, significantly prolonged the K+-evoked signals observed in both the granule/Purkinje cell and molecular layers. These data, taken together with earlier reports on the electrophysiological responses to activation of cerebellar noradrenergic inputs, support the conjecture that in vivo electrochemical recording methods have the sensitivity and spatial resolution for studies of functional monoamine release from brain regions that have a diffuse or laminated monoamine innervation.

Action Potentials↗
PubMed1987

Myocardium and cortex cerebri xenografts transplanted into the anterior chamber of the eye of athymic rats: a morphologic and electrophysiologic profile.

Heart atria and cortex cerebri from fetal rabbits (E14 and E18, respectively) were grafted into the anterior eye chamber of anesthetized athymic nude rats and allowed to mature for 2-11 weeks. All grafts received a rich vascular supply from the host iris. Atrial transplants survived well but showed no significant growth while cortex grafts increased in size an average of 320%. Spontaneous action potentials were recorded from cellular elements in both tissues and, in the case of the atria, were accompanied by observable contractions. Functional cholinergic innervation from the autonomic ground plexus of the iris was elicited in both types of grafts by phasic retinal illumination. No evidence of immunologic rejection was found by histological analysis. Taken together, these data suggest that athymic rats may provide an appropriate host environment to study transplants of the central nervous and peripheral tissue from immunologically otherwise incompatible mammalian species.

Action Potentials↗
PubMed1987

Electrophysiological effects of phencyclidine in the medial prefrontal cortex of the rat.

The effects of local applications of phencyclidine (PCP) and dopamine (DA) on neurons of the medial prefrontal cortex were investigated using single unit recording techniques. The activity of the majority of cells in the deeper layers of the medial prefrontal cortex was depressed by both phencyclidine and DA, whereas increases, as well as decreases, in the firing rates were observed in cells located in the superficial cortical layers. The stereospecificity of the responses of deeper cells to phencyclidine was demonstrated using the enantiomers of 1-(-1-phenylcyclohexyl)-3-methylpiperidine (PCMP). Phencyclidine was found to be 1.5 times more potent than (+) PCMP and 3 times more potent than (-) PCMP. Finally, the DA receptor antagonist fluphenazine, blocked the phencyclidine-elicited depressions of unit activity in the deep prefrontal cortex. Taken together, the data indicate that the DA-like effects of phencyclidine on neurons of the medial prefrontal cortex are mediated by DA receptors and provide pharmacological support for the idea that psychomotor stimulant drugs have specific actions on targets of the ventral tegmental area (A10) dopamine system.

Animals↗
PubMed1987

Desipramine and noradrenergic neurotransmission in aging: failure to respond in aged laboratory animals.

Deficiencies in noradrenergic neurotransmission have been found in the central nervous system of aged laboratory animals. The purpose of the present study was to determine if tricyclic antidepressants, such as desipramine, can overcome the diminished noradrenergic neurotransmission found in these animals. Using electrophysiological techniques, noradrenergic neurotransmission was examined in the cerebellar cortex of rats, a model system which has been used extensively to characterize the effects of norepinephrine in the central nervous system. The discharge rate of cerebellar Purkinje neurons is very sensitive to changes in the noradrenergic input from the nucleus locus coeruleus. In this model system in young rats, treatment with desipramine slowly augments noradrenergic neurotransmission over several weeks. Similar treatment in aged animals caused no increase in the age-related deficient noradrenergic neurotransmission. The decline in efficacy of desipramine with age could not be accounted for by differences between young and old rats in the distribution of the drug. Failure of desipramine to be effective in older rats may reflect the insensitivity of aged neurons to norepinephrine itself, so that treatment strategies which increase the amount of nerepinephrine released onto these neurons may be ineffective. The findings may have implications for the use of tricyclic antidepressants in aged depressed patients.

Action Potentials↗
PubMed1987

Selective antagonism of nicotine actions in the rat cerebellum with alpha-bungarotoxin.

Nicotine, locally applied to identified neurons in the rat cerebellar cortex, excites inhibitory interneurons, but depresses the discharge of Purkinje cells. Alpha-bungarotoxin blocked the excitatory actions of nicotine on the inhibitory interneurons. The antagonism of nicotine excitatory actions is largely irreversible and also insurmountable with higher doses of nicotine. The antagonism by alpha-bungarotoxin is, in addition, selective since there is no blockade of the inhibitory actions of nicotine on Purkinje neurons. The present data suggest that the excitatory actions of nicotine on inhibitory interneurons are mediated by neuromuscular-type nicotinic receptors in the cerebellum. Moreover, the present data also supports the hypothesis of multiple nicotinic sites of action in mammalian brain.

Action Potentials↗
PubMed1987

Toxic effects of lead in the developing nervous system: in oculo experimental models.

Modern man is chronically exposed to lead in the biosphere at levels several orders of magnitude higher than the natural level that once existed. There is much concern about the possible adverse effects of this population-wide, low-level lead exposure, particularly on the developing organism, wherein the central nervous system may be one primary target. We have developed in oculo test systems, which permit temporal and spatial discrimination of possible effects of lead and other potential neurotoxic agents in the environment on the developing central nervous system as well as on different types of peripheral nerves in the adult. In one experimental protocol, defined areas of the fetal rat brain are grafted to the anterior chamber of the eye of adult rat recipients that are exposed to lead. Such grafts will become vascularized from the host iris and continue developing in oculo. Thus, grafted brain tissue and host brain will share circulation and therefore be exposed to similar amounts of lead. Studies of cerebellar grafts revealed that, although there was a normal gross cytological development in the presence of lead, there was a marked and permanent impairment of spontaneous discharge rates of the grafted Purkinje neurons as observed with electrophysiological techniques long after cessation of lead treatment. The host Purkinje neurons were not affected. A similar, although less dramatic, impairment of cerebellar function could be subsequently demonstrated in intact animals when newborn rats were given lead during the first 20 days of life and studied as adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Heterogeneity of nicotine actions in the rat cerebellum: an in vivo electrophysiologic study.

Much controversy surrounds the actions of nicotine on mammalian central neurons, especially with respect to the question of presence of multiple nicotine receptors and with respect to similarities of responses to those induced by acetylcholine (ACh). To resolve some of these complexities, the authors determined the effects of pressure-ejected nicotine on identified neurons in the cerebellar cortex of Sprague-Dawley rats under urethane anesthesia. Purkinje cells and interneurons were identified by their anatomical localization, discharge characteristics and responses to electrical stimulation of superficial parallel fibers. Locally applied nicotine altered single-unit activity in a manner strictly dependent on cell type. Pressure-ejected nicotine inhibited Purkinje cells (50/51) and excited cerebellar interneurons (22/22). The effects of nicotine on cell discharge rate were probably receptor mediated because "classical" nondepolarizing nicotinic antagonists selectively blocked the agonistic actions of nicotine. A curare-sensitive site (neuromuscular type) was found to mediate the excitatory effects of nicotine, and a hexamethonium-sensitive site (ganglionic type) was found to mediate the inhibitory effects of nicotine. ACh mimicked the effects of nicotine on both cell classes although muscarinic interactions were also observed. The inhibitory effects of ACh on Purkinje cells were antagonized by the ganglionic blocker hexamethonium only if muscarinic receptors were simultaneously blocked via systemic administration of scopolamine. The excitatory effects of ACh on interneurons, on the other hand, were antagonized by the neuromuscular blocker curare even in the absence of a muscarinic antagonist. No interactions of curare and hexamethonium were observed with the amino acid transmitters gamma-aminobutyric acid (Purkinje cells) and glutamate (interneurons).

Acetylcholine↗
PubMed1986

Diminished interaction of norepinephrine with climbing fiber inputs to cerebellar Purkinje neurons in aged Fischer 344 rats.

The ability of norepinephrine (NE) to modulate climbing fiber activation of complex spike discharge in cerebellar Purkinje neurons was compared in young (3-6 months) and aged (18-20 months) Fischer 344 rats. In young rats, NE selectively inhibits spontaneous activity while climbing fiber evoked activity remains intact or increased. NE also increases the probability of observing 4 bursts of full-sized action potentials rather than partially inactivated action potentials in the complex spike. In older rats, both of these modulatory actions of NE on climbing fiber complex spike activation are markedly diminished. These data support the concept that age-related reductions in catecholamine modulation of synaptic inputs may contribute to CNS dysfunction found in senescence.

Aging↗