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J Grenhoff

Publications and source records attributed to J Grenhoff.

32 records · Page 2Linked to original sources
PubMed1989

Clonidine modulates dopamine cell firing in rat ventral tegmental area.

The effect of clonidine (5-20 micrograms/kg i.v.) on the activity of single, identified dopamine neurons in the ventral tegmental area of the mesencephalon was studied in chloral hydrate-anesthetized male rats. Clonidine regularized cell firing without affecting the firing rate of the neurons. This effect was blocked by idazoxan (0.5 mg/kg i.v.) or yohimbine (1.0 mg/kg i.v.), but not by phentolamine (1.0 mg/kg i.v.), indicating that clonidine acts at central alpha 2-adrenoceptors. Idazoxan or yohimbine alone produced deregularization and excitation of cell firing. Pretreatment with reserpine (5 mg/kg s.c.) 4 h before the experiment abolished the neuromodulatory effect of clonidine. Thus, the regularization of ventral tegmental area dopamine cell firing by clonidine is indirect and dependent on endogenous monoamines in brain, and, in principle, a tonic adrenergic control of DA cell firing pattern is indicated. The regularization of DA cell activity produced by clonidine may underlie certain therapeutic neuropsychiatric actions of the drug.

Action Potentials↗
PubMed1989

Peripheral induction of burst firing in locus coeruleus neurons by nicotine mediated via excitatory amino acids.

The effect of systemic nicotine administration (50 micrograms kg-1 i.v.) on the activity of brain noradrenaline neurons in the locus coeruleus (LC) of chloral hydrate-anesthetized rats was analyzed with single cell recording techniques and quantitative computer assessment of firing rate, degree of bursting, and regularity of firing. Nicotine caused an increased firing rate of the cells, with an average time of onset of 1.7 s. An increase in burst activity was observed, as well as deregularization of the firing pattern. Intraventricularly administered kynurenic acid (1 mumol), an antagonist of excitatory amino acids (EAA), did not change the firing rate of the LC cells, but did induce a marked regularization of their firing pattern into a pacemaker-like activity and completely abolish burst firing. The EAA antagonist also blocked all of the above effects of nicotine on the LC neurons as well as their typical burst-activation response to a peripheral, noxious stimulus such as paw-pinch. Since the circulation time in the rat is about 20 s, these results provide unequivocal evidence for a peripheral site of origin for the rapid LC activation induced by systemic nicotine administration. The data also allow the conclusion that the nicotine-induced LC activation is indirect and dependent on EAA in brain. Our results provide evidence for a tonically active EAA input to the LC, being of importance for induction of changes in the spontaneous, pacemaker activity of LC neurons into burst firing or more irregular firing patterns. It is suggested that the LC activation by nicotine may be significant in relation to tobacco dependence.

Action Potentials↗
PubMed1989

Ritanserin, a 5-HT2 receptor antagonist, activates midbrain dopamine neurons by blocking serotonergic inhibition.

The effect of systemic administration of ritanserin (R 55667), a 5-hydroxytryptamine (5-HT2) receptor antagonist, on midbrain dopamine (DA) neurons was studied with single cell recording techniques in the chloral hydrate anesthetized male rat. Dopamine cells of the zona compacta, substantia nigra (ZC-SN) and the ventral tegmental area (VTA) were identified by established criteria. Ritanserin (0.5-2.0 mg/kg, IV) dose-dependently increased both the burst firing and firing rate of the midbrain DA neurons. These effects were prevented by endogenous 5-HT depletion through pretreatment with the 5-HT synthesis inhibitor para-chlorophenylalanine (PCPA, 300 mg/kg, IP, x3), which did not significantly alter the firing characteristics of the midbrain DA cells when given alone. These results suggest that 5-HT exerts an inhibitory control of midbrain DA cell activity mediated by 5-HT2 receptors. The stimulatory effect of ritanserin on midbrain DA systems might contribute to some of its clinical effects, such as improvement of mood, drive and motivation as well as its therapeutic actions in parkinsonism and type II schizophrenia.

Action Potentials↗
PubMed1989

Pharmacology of nicotine.

In recent years progress in basic neuropsychopharmacology and clinical addiction research have allowed the conclusion that tobacco smoking essentially represents an addiction to nicotine. Parallel to this work, experimental research in biochemistry, physiology and pharmacology has provided detailed descriptions of the structure and function of the nicotinic receptor, the biologic mediator of the many actions of nicotine. This article reviews current knowledge of nicotinic mechanisms in the peripheral and central nervous systems as well as some implications for the notion of smoking as an addiction to nicotine. In particular this review will focus on the effects of nicotine on brain dopamine and noradrenaline systems since these neuronal systems appear to be crucially involved in the rewarding and stimulant effects of addictive drugs.

Animals↗
PubMed1988

Does treatment with haloperidol for 3 weeks produce depolarization block in midbrain dopamine neurons of unanaesthetized rats?

Treatment of rats with haloperidol, 0.5 mg/kg SC daily for 3 weeks, did not increase the concentration of dopamine in the dopamine-rich nuclei of the forebrain apart from a small effect in the olfactory tubercle. Cessation of the nerve impulse flow in the ascending dopamine neurons induced by gamma-butyrolactone caused an approximately twofold increase in the dopamine levels of both haloperidol-treated and control rats. The results are hard to reconcile with the notion of haloperidol-induced depolarization block, i.e., cessation of impulse flow in the majority of midbrain dopamine neurons of unanaesthetized rats.

4-Butyrolactone↗
PubMed1988

Clonidine regularizes substantia nigra dopamine cell firing.

The effects of clonidine on the activity of single substantia nigra dopamine neurons were studied in the chloral hydrate anesthetized rat. Although clonidine did not affect the firing rate of the cells, it regularized the firing pattern and decreased burst firing at 2-8 micrograms kg-1 i.v. These effects were antagonized by the alpha 2-antagonist yohimbine. Yohimbine (1.0 mg kg-1) deregularized the firing pattern and increased the firing rate as well as the burst firing. The regularization produced by clonidine is discussed in terms of synaptic efficacy. The results might explain the therapeutic effects of clonidine in certain neuropsychiatric disorders.

Action Potentials↗
PubMed1988

Firing patterns of midbrain dopamine neurons: differences between A9 and A10 cells.

Dopamine neurons of the substantia nigra (A9) and the ventral tegmental area (A10), giving rise to the nigrostriatal and mesolimbic dopamine pathways, respectively, are commonly supposed to show similar electrophysiological activity. There are, however, instances where the two systems are differently modulated. To assess possible physiological differences in the neuronal activity of A9 and A10 neurons, randomly sampled single cells were extracellularly recorded in the chloral hydrate-anaesthetized male rat. In addition to firing rate, the degree of burst firing and the regularity of firing were quantitatively analysed. Our results show that although A9 and A10 do not differ in firing rates, A10 neuronal activity is markedly less regular and shows a higher degree of burst firing, as judged from analysis of inter-spike time interval histograms. Mean burst firing values were 3% for the A9, and 23% for the A10 neurons. Regularity was described by variation coefficients of inter-spike time interval histograms. The mean variation coefficient was 38.4% in the A9 group and 63.8% in the A10 group, i.e. the A10 neuronal firing was less regular. The difference in regularity is partly, but not fully, dependent on the difference in burst firing. Previous biochemical and physiological studies strongly support the functional significance of modulatory changes in midbrain dopamine-cell firing patterns. Since the firing pattern of midbrain dopamine cells seems to be controlled by synaptic inputs, our results indicate a higher tonic modulatory influence on the A10 than on the A9 neurons. Thus the present results imply the pharmacological possibility of preferentially affecting A10 versus A9 dopamine cell function.

Action Potentials↗
PubMed1986

Nicotinic effects on the firing pattern of midbrain dopamine neurons.

The effects of systemic administration of nicotine or the nicotinic antagonist mecamylamine on the midbrain dopamine (DA) systems of the rat were studied with single cell recording techniques. Dopamine cells of the zona compacta, substantia nigra (ZC-SN) and the ventral tegmental area (VTA) were identified by their characteristic action potentials, antidromic stimulation methodology and conventional histological procedures. Firing rates as well as firing patterns were determined from computer-generated interspike interval histograms describing burst-firing in relation to single-spike firing. A larger proportion of burst-firing DA cells was found in the VTA when compared with the ZC-SN area. (-)-Nicotine bitartrate (0.5 mg kg-1 i.p.) not only increased the firing rate of ZC-SN neurons but also the amount of burst firing of the ZC-SN neurons and VTA neurons, respectively. Mecamylamine HCl (4.0 mg kg-1 i.p.) decreased the firing rate of VTA cells which, in principle, indicates a tonic nicotinic input in this area. The increase in firing rate of central DA neurons following nicotine administration was found to be associated with increased bursting of the burst firing cells whereas, in contrast, the non-bursting neurons did not respond with burst-firing. Generally, the correlation between nicotine induced changes in firing rate and in burst-firing activity, respectively, was found to be low for midbrain DA neurons. These observations, in conjunction with the previous demonstration of nicotinic receptors in these areas, indicate the existence of a nicotinic input, specifically regulating the firing pattern of these central DA cells. This neuromodulatory effect of nicotine may be significant for its behavioural stimulant action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗