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P M Groves

Publications and source records attributed to P M Groves.

At least 91 records · Page 5Linked to original sources

Sites of action of amphetamine intrinsic to catecholaminergic nuclei: catecholaminergic presynaptic dendrites and axons.

1. It is now well established that the behavioral actions of amphetamine, especially locomotor and stereotyped behaviors, are dependent in part upon the release of catecholamines in the central nervous system. 2. A variety of empirical evidence has established that the release of catecholamines by amphetamine leads to changes in neuronal activity in regions postsynaptic to catecholaminergic nerve terminals. In addition, release of catecholamines is accompanied by a marked inhibition of neuronal firing in catecholaminergic neurons. 3. At least two conceptions have been advanced to account for this marked decrease in catecholaminergic neuronal activity. (a) In one of these, release of catecholamines from presynaptic terminals is thought to lead to a compensatory decrease in neuronal firing rate by means of a postsynaptic neuronal feedback loop from regions innervated by catecholaminergic neurons. (b) In the other, decreased neuronal activity is hypothesized to result from local release of catecholamines onto or near catecholaminergic neuronal dendrites and somata, a phenomenon that has been characterized as self-inhibition. 4. For dopaminergic neurons, recent biochemical, neuropharmacological and neuroanatomical evidence suggests that the latter process could be subserved by dopamine released from dopaminergic neuronal dendrites, i.e., "presynaptic" dendrites.

Amphetamine↗

Alterations of spontaneous neuronal activity in the caudate-putamen, nucleus accumbens and amygdaloid complex of rats produced by D-amphetamine.

Changes in spontaneous neuronal activity in the caudate-putamen, accumbens nucleus and amygdaloid complex of immunobilized, locally anesthetized rats were recorded following intraperitoneal injection of 2.5 mg/kg d-amphetamine sulfate. In each site, d-amphetamine typically produced a prolonged depression of firing rate which, in most cases, occurred after an inital, brief potentiation of activity. However, the onset of the amphetamine-induced depression occurred signficantly later in the amygdala. Subsequent IP administration of either 5.0 mg/kg chlorpromazine or 2.0 mg/kg haloperidol reversed, to varying degrees, the amphetamine-induced depression of neuronal activity in each area. These results are discussed in terms of the known biochemical effects of amphetamine on catecholaminergic transmission and the alleged role of the nigro-neostriatal mesolimbic dopamine systems in the amphetamine behavioral response.

Amygdala↗

Monoaminergic synapses, including dendro-dendritic synapses in the rat substantia nigra.

Intraventricular administration of 1 or 2 mg of the osmiophilic "false transmitter" 5-hydroxydopamine (5-OHDA) was used to label monoamine storage and release sites in the rat substantia nigra. Vesicles containing unusually dense cores indicative of the presence of the marker were seen forming from the Golgi apparatus in the cell bodies of medium-sized neurons of the substantia nigra, pars compacta, and from smooth endoplasmic reticulum in the dendrites of those neurons and in small unmyelinated axons of unknown origin. In serial sections, both axons and dendrites containing synaptic vesicles marked with 5-OHDA were seen to form synapses "en passage" in pars compacta, and some presynaptic dendrites containing vesicles filled by the marker were also observed to form contacts with dendrites in pars reticulata. The only identified postsynaptic elements engaging in monoaminergic synapses in the substantia nigra were dendrites of medium-sized pars compacta neurons.

Animals↗

The substantia nigra of the rat: a Golgi study.

Three variants of the Golgi method were employed to examine the cell types, their dendritic fields and organization and axonal trajectories within the substantia nigra of albino and hooded rats. In both sagittal and coronal sections, large, medium and small neurons were classified on the basis of soma size, extent of dendritic fileds and dendritic caliber. In general nigral cells have three to five primary dendrites that branch relatively infrequently. Some dendrites of all cell types have thinly scattered spines or varicosities. Small cells, found in all areas of the nucleus, have thin dendrites and small, nondirectional dendritic fields. These are considered to be interneurons. The medium cells found in pars compacta, presumed to be the dopaminergic cells of the nigroneostriatal pathway, send long dendrites into pars reticulata perpendicular to the course of pars compacta. In addition, these cells have a number of dendrites which remain in pars compacta. These cells have axons that run medio-dorsally. No axon collaterals were detected. Both large and medium cells are found in pars reticulata. Cells in the dorso-medial aspect of pars reticulata orient rostro-caudally and roughly perpendicular to the course of pars compacta, while cells in the peripeduncular area show a strict orientation which is parallel to the crus cerebri. Some pars reticulata cells emit axon collaterals while others remain unbranced for their observable lenght. Both large and medium cells are also seen in pars lateralis. These cells send long dendrites ventrally into pars reticulata where they run parallel to the crus cerebri, while some shorter dendrites remain in pars lateralis. In total, the substantia nigra appears to have a layered organization: the superior layer is the cellular pars compacta, the second is the dorso-medial area of pars reticulata where both pars compacta and pars reticulata dendrites run rostro-caudally and dorso-ventrally and the third layer is the peripeduncular region where dendrites from all areas run parallel to the crus cerebri.

Animals↗

Possible mechanisms involved in the stereotyped behavior elicited by amphetamine.

In a variety of animals, amphetamine administration produces an increase in locomotor behavior and an induction of repetitive, stereotyped behaviors. There is now considerable evidence to suggest that the induction of stereotyped behaviors is accomplished, in part, by alterations in catecholaminergic transmission in the central nervous system. By recording the spontaneous activity of neurons in the rat brain substantia nigra, reticular formation, basal ganglia, and elsewhere during systemic administration of amphetamine and related drugs, or during administration by means of microinfusions directly into these brain regions, relationships may be drawn between the biochemical and behavioral effects of these drugs and drug-induced changes in neuronal activity in the central nerovous system. Current evidence, for example, suggests that amphetamine produces an inhibition of neuronal activity in the neostriatum and pars compacta of the substantia nigra by means of dopamine released from dopaminergic terminals in the neostriatum and dopaminergic dendrites in the substantia nigra respectively. In addition, current evidence suggests the possibility of a GABA-mediated functional antagonism between excitatory cortical and/or thalamic input to the neostriatum and dopaminergic input from the substantia nigra which could be involved in the apparently mutually exclusive occurrence of amphetamine-induced locomotion and stereotyped behaviors that follow amphetamine administration. Such evidence may also have relevance to a variety of behavioral disorders involving the basal ganglia and catecholaminergic transmission in the central nervous system.

Amphetamine↗

Enhancement of effects of dopaminergic agonists on neuronal activity in the caudate-putamen of the rat following long-term d-amphetamine administration.

Amphetamine- and apomorphine-induced changes in the activity of neurons in the caudate-putamen of paralyzed, locally anesthetized rats were recorded in animals pretreated with 2.5 mg/kg d-amphetamine sulphate for 6, 18 or 36 days, or in animals pretreated with saline for 36 consecutive days. In saline-pretreated animals, 2.5 mg/kg d-amphetamine sulphate (IP) produced an initial, brief potentiation of neuronal firing that was followed by a marked depression of neuronal activity lasting for approximately 35 to 110 min after injection. In amphetamine-pretreated animals, this depression of neuronal activity to the same dose of the drug was markedly prolonged, especially in animals given 36 consecutive days of d-amphetamine pretreatment. A similar enhancement occurred in response to 0.25 mg/kg apomorphine (IP) in animals pretreated with amphetamine for 36 days compared to saline-pretreated control animals. These results are discussed in relation to the known behavioral and biochemical effects of acute and long-term amphetamine administration.

Action Potentials↗

Differential effects of the optical isomers of amphetamine on neuronal activity in the reticular formation and caudate nucleus of the rat.

The activity of neurons in the caudate nucleus and reticular formation was recorded following intraperitoneal injection of the optical isomers of amphetamine. In general, D-amphetamine sulfate (2.0 mg/kg) produced an initial increase in firing rate of neurons in the caudate nucleus approximately 8-10 min following intraperitoneal injection, and a subsequent depression of firing rat which lasted for a period of time of from 70 to 120 min. Similar injections of L-amphetamine sulfate produced only a depression of activity in the caudate nucleus which was less marked and of lesser duration. Mephentermine sulfate (6.0 mg/kg), a peripheral sympathomimetic, did not produce these effects. Both D-amphetamine and L-amphetamine sulfate at the same dose produced an increase in firing rate of neurons in the reticular formation, although that produced by the L-isomer was less marked and of lesser duration. Mephentermine sulfate also produced an increase in reticular formation neuronal activity comparable to that produced by L-amphetamine sulfate. In some cases, neuronal activity was held for prolonged periods of time following injection. In the caudate nucleus, a rebound increase in firing rate was observed following the marked depression produced by both isomers of amphetamine. A rebound depression of activity was observed in the reticular formation following the initial increase in neuronal activity produced by these drugs. The results are discussed in terms of the known biochemical and behavioral effects of the stereoisomers of amphetamine.

Amphetamine↗

Intracellular recordings from phycomyces.

Intracellular recordings from the giant sporangiophore of Phycomyces stage II were obtained. The mean transmembrane potential for 30 observations was -119.9 millivolts (negative inside), and it did not change either as a result of a light stimulus or during dark adaptation. Injected depolarizing and hyperpolarizing step currents and steady currents did not produce any avidence of spike activity. We conclude that light transduction and dark adaptation in Phycomyces are not based on alterations of the transmembrane potential.

Journal Article↗