Biomedical subjects

H C Moises

Publications and source records attributed to H C Moises.

At least 37 records · Page 2Linked to original sources

PubMed1992

Electrophysiological and morphological properties of rat basolateral amygdaloid neurons in vitro.

Electrophysiological and morphological properties of neurons in the rat basolateral amygdala (BLA) were assessed using intracellular recordings in brain slice preparations. The vast majority of cells studied were identified as pyramidal cells on the basis of their accommodation response and by a prominent afterhyperpolarization that followed a current-evoked burst of action potentials. The second class of cells consisted of late-firing neurons that were distinguished electrophysiologically by their very negative resting membrane potential (-82 mV) and conspicuous delay in the onset of spike firing in response to depolarizing current injection. The third class of cells, termed fast-firing neurons, possessed many of the features of intrinsic inhibitory interneurons found elsewhere in the brain. These included very brief action potentials (0.7 msec), a relatively depolarized resting membrane potential (-62 mV), and spontaneous firing at a high rate and the absence of spike frequency accommodation. Intracellular labeling with Lucifer yellow of electrophysiologically identified pyramidal and late-firing cells showed them to have pyramidal to stellate cells bodies and spine-covered dendrites. Although having an overall pyramidal-like morphology, late-firing neurons possessed cells bodies and dendritic fields that were smaller than those of pyramidal cells. Lucifer yellow-labeled fast-firing neurons had a nonpyramidal morphology, with somata that were spherical to multipolar in shape and spine-sparse or aspiny dendrites. The morphological features of these cells corresponded closely to those of GABA-containing interneurons that have been described previously in the rat BLA using immunohistochemical techniques (McDonald, 1985b). Thus, it seems likely that activation of fast-firing neurons underlies inhibitory synaptic events that are recorded in the rat BLA. Our data support the conclusion derived from previous anatomical studies that pyramidal neurons constitute the predominant cell type in the BLA and function as projection neurons in this region of the amygdala. The determination of whether late-firing cells constitute a unique class of projection neurons distinct from pyramidal cells must await the outcome of studies in which the anatomical terminations of this cell type are specified.

Action Potentials↗

PubMed1991

Modulatory actions of norepinephrine on neural circuits.

A spectrum of studies has been conducted on a single aspect of NE function in which, through a beta-one receptor activation, NE appears to mediate a degree of physiological control over the gain of GABA mediated inhibition. It is significant that this single effect has been observed in numerous interrelated preparations ranging from single isolated Purkinje cells from young rats to adult Purkinje cells in awake locomoting rats. With respect to the functional conse-quences of these effects, our best current speculation as to "what NE does" is that NE acts to regulate the strength of these tuned gating mechanisms in both cerebral and cerebellar cortices. There are numerous unanswered questions raised by the past work. One pressing issue is - when and for what reason in normal function does the modulation take place? When does NE release normally occur (is it phasic or tonic), and which of the demonstrated actions appears and for how long in relation to period of receptor activation? Does NE release cause the circuit to "react" to conditions which need "improved neurocomputation" or does NE stabilize the circuit to react predictably in the face of stress? Finally, what is the molecular sequence of events between receptor activation and an alteration of GABA receptor channel opening? What additional molecular control mechanisms exist and how can the diverse inhibitory and modulatory phenomena be reconciled, both short and long term? Issues are defined which need to be clarified at all levels of the current skeleton of basic understanding. Our prediction is that pursuit of these issues will benefit from an exchange of insight gained from investigations at all levels.

Animals↗

PubMed1991

The cerebellar norepinephrine system: inhibition, modulation, and gating.

A series of studies has been conducted to determine the mode of action on the cerebellar cortical circuitry of the norepinephrine (NE)-containing afferents from the locus coeruleus. NE has been known to exert an "inhibitory" action on the background firing observed in Purkinje cells, due presumably to a shift in conductances favoring hyperpolarization. An additional independent action at low threshold appears to be an enhancement of GABA, the inhibitory transmitter of cerebellar interneurons. Recent whole-cell patch-clamp studies on isolated Purkinje cells indicate that exposure to NE increases the chloride current caused by transient pulses of GABA applied iontophoretically. NE applied to Purkinje cells in the parafloccular lobule during stimulation by moving visual patterns revealed the capacity either to "gate" signals initially not expressed, or to amplify the gain of phasic excitations. The control of emergent circuit functions may be the functional consequence of the multiple modulatory functions of NE.

Action Potentials↗

PubMed1991

Exogenous NGF affects cholinergic transmitter function and Y-maze behavior in aged Fischer 344 male rats.

Chronic ICV administration of NGF stimulates the activity of the cholinergic neuronal markers, HACU and ChAT, as well as the evoked release of both endogenous and newly synthesized acetylcholine in the brain of aging Fischer 344 male rats. However, the pattern of cholinergic phenotype stimulation indicates an age-related differential regulation of ChAT, HACU, and ACh release between specific brain areas, with the largest effects found in the striatum. NGF treatment also increases the effectiveness of neurotransmission between basal forebrain cholinergic neurons and postsynaptic amygdaloid target neurons. The stimulation of central cholinergic transmitter function after NGF treatment affects behavior in a Y-maze brightness discrimination paradigm. NGF treatment does not affect the cognitive measure of brightness discrimination, but reduces the number of avoidance attempts, a measure of motor function.

Acetylcholine↗

PubMed1991

Blood to brain sodium transport and interstitial fluid potassium concentration during early focal ischemia in the rat.

During partial ischemia, sodium and potassium ions exchange across the blood-brain barrier, resulting in a net increase in cations and brain edema. Since this exchange is likely mediated by specific transporters such as Na,K-ATPase in the capillary endothelium and because brain capillary Na,K-ATPase activity is stimulated by increased extracellular potassium in vitro, this study was designed to determine if the rate of blood to brain sodium transport is increased in ischemic tissue having an elevated interstitial fluid potassium concentration ([K]ISF) in vivo. Sprague-Dawley rats were studied between 2-3 h after occlusion of the right middle cerebral artery. To identify where cortical tissue with an elevated [K]ISF could be sampled for transport studies, the regional pattern of cerebral blood flow and [K]ISF was obtained in a group of 17 rats using hydrogen clearance and potassium-selective microelectrode techniques. We observed severely elevated [K]ISF (greater than 10 mM) when CBF was less than 20 ml 100 g-1 min-1 and mildly elevated levels at CBF between 20-45 ml 100 g-1 min-1. In a second group of seven rats, permeability-surface area products (PS products) for 22Na and [3H]alpha-aminoisobutyric acid ([3H]AIB) were determined in ischemic cortex with elevated [K]ISF and in nonischemic cortex. The PS products for AIB were similar in both tissues (2.2 +/- 0.7 and 2.1 +/- 0.4 microliters/g/min) while the PS products for sodium was significantly increased in the ischemic tissue (1.5 +/- 0.2 and 2.4 +/- 1.1 microliters/g/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoisobutyric Acids↗

PubMed1990

Potassium activation of the Na,K-pump in isolated brain microvessels and synaptosomes.

Brain capillary endothelial cells play an important role in ion homeostasis of the brain through the transendothelial transport of Na and K. Since little is known about the regulation of ion transport in these cells, we determined the effect of extracellular potassium concentration ([K]o) on the kinetics of the Na,K-pump in isolated cerebral microvessels using both K uptake and Na efflux as measures of pump activity. In addition, we studied K activation of K uptake into synaptosomes under similar conditions to compare this neuronal system to the capillary. When microvessels were preloaded with 22Na by 30 min incubation in K-free buffer, efflux of 22Na into buffer with varying [K]o was dependent on [K]o and inhibited by 7 mM ouabain. This activation of Na efflux was half maximal at 4.2 mM [K]. Ouabain-sensitive K uptake was also half maximally stimulated by a similar [K] in both Na loaded and non-loaded microvessels. In contrast, K uptake into synaptosomes was half maximal at 0.47 mM K. These results demonstrate that both active Na efflux and K uptake into microvessels in vitro are dependent on [K]o in the physiological range. In contrast, synaptosomal K uptake is near maximal at 3 mM K. This suggests that increases in brain [K]o may stimulate ion transport across the cerebral capillary, but will have little effect on Na,K-pump activity in neurons.

Animals↗

PubMed1990

Modification of the visual response properties of cerebellar neurons by norepinephrine.

Extracellular recordings were conducted in the paraflocculus of anesthetized Long-Evans pigmented rats to determine how ionotophoresis of norepinephrine (NE) affects the responsiveness of individual Purkinje cells and interneurons to presentations of visual stimuli within their visual receptive fields. Presentations of moving or stationary visual stimuli during the control (pre-NE) period elicited simple spike excitations or inhibitory responses in slightly more than one-half (55%, n = 32) of the cells tested (20 of 38 Purkinje cells, 12 of 20 interneurons). The predominant effect of NE iontophoresis was to improve visually evoked responses in those neurons which showed modulations in their simple spike discharge to control presentations of visual stimuli. A clear enhancement of visual responses by NE (i.e., absolute increase over control) was observed in 18 of the units, and in 12 of the 14 remaining cells, reductions in stimulus-bound discharge during catecholamine iontophoresis were accompanied by much larger depressions in background activity, resulting in a net enhancement in the ratio of signal-to-noise. NE differentially affected responses to stimulus movement in the preferred and non-preferred direction in one-third of these neurons, such that directional selectivity was increased. However, the orientation bias of individual units was unchanged by NE. Iontophoretic application of the beta-adrenergic antagonist sotalol but not the alpha-adrenergic antagonist phentolamine blocked these facilitating noradrenergic effects. An additional feature of noradrenergic action was revealed in tests conducted in 26 cells which did not respond to control presentations of visual stimuli. Iontophoresis of NE resulted in the elicitation of visual responses in 11 of these units, suggesting the possibility that NE might act in some cases to gate the efficacy of subliminal synaptic input conveyed by classical afferent channels. It is proposed that an important aspect of noradrenergic action within local cerebellar circuits might be to refine the receptive field properties of individual neuronal elements and thereby improve information flow through the cerebellum.

Action Potentials↗

PubMed1990

Dynorphin A and cAMP-dependent protein kinase independently regulate neuronal calcium currents.

The kappa-selective opioid peptide dynorphin A (DYN) inhibits neuronal adenylate cyclase activity and reduces neuronal voltage-dependent calcium currents. It is not yet known, however, whether the regulation of calcium channel activity is dependent on or independent of the adenylate cyclase/cAMP system. We used the whole-cell variation of the patch clamp technique to show that DYN reversibly reduced, in a naloxone-sensitive manner, calcium currents in acutely dissociated rat nodose ganglion neurons. DYN slowed the rate of current activation and had a greater effect on currents evoked from relatively negative holding potentials. These actions were mimicked by guanosine 5'-[gamma-thio]triphosphate, which activates GTP-binding proteins (G proteins), and were blocked by pretreatment with pertussis toxin, which inactivates Gi- and Go-type G proteins. In contrast, calcium currents recorded in the presence of the catalytic subunit of the cAMP-dependent protein kinase (AK-C), included in the recording pipette, increased in magnitude throughout the recording. DYN was applied to neurons before and after the effect of AK-C became apparent; the reduction of calcium currents by DYN was greater in the presence of AK-C than in its absence. We conclude that the acute reduction of neuronal calcium currents by DYN occurred by means of activation of pertussis toxin-sensitive Gi- or Go-type G proteins. The persistence of the action of DYN in the presence of AK-C indicates, however, that this effect was independent of a reduction of the activity of the adenylate cyclase/cAMP system and suggests in addition that phosphorylated channels may be preferentially inhibited by DYN.

Adenylate Cyclase Toxin↗

PubMed1989

Electrophysiological responsiveness to isoproterenol in rat hippocampal slices correlates with changes in beta-adrenergic receptor density induced by chronic morphine treatment.

The effects of chronic morphine treatment and morphine withdrawal on beta-adrenergic receptor density and electrophysiological responsiveness in rat hippocampus were examined. Chronic treatment of rats with morphine for 14 days resulted in a 19% increase in the number of beta-adrenergic receptors in hippocampus, as measured by the binding of the specific antagonist [3H]dihydroalprenolol (DHA). In comparison, the number of specific binding sites for [3H]DHA was decreased 27% in hippocampus in morphine-withdrawn animals, compared to saline-treated controls. These alterations in beta-adrenergic receptor density were not accompanied by a significant change in the dissociation constant (Kd) for [3H]DHA or in the inhibitory constants (Ki) for the displacement of the [3H]-antagonist by either norepinephrine or isoproterenol. Electrophysiological experiments in the in vitro hippocampal slice preparation revealed that responses to threshold as well as maximal concentrations of isoproterenol were significantly enhanced in morphine-dependent animals, compared to controls, whereas electrophysiological responsiveness to maximal concentrations of isoproterenol was decreased in slices from morphine-withdrawn rats. The results of this study indicate that beta-adrenergic receptors in hippocampus are up-regulated during the development of morphine dependence and down-regulated during opiate withdrawal. These changes in hippocampal beta-adrenergic receptor density are likely to be of functional relevance since they are manifested in a corresponding increase and decrease, respectively, in electrophysiological responsiveness to an exogenously administered beta-adrenergic receptor agonist.

Action Potentials↗

PubMed1989

Changes in alpha 2-adrenoceptor number and function in brains of morphine-dependent rats.

The effects of long-term treatment of rats with morphine sulfate were assessed upon the specific binding of [3H]clonidine to alpha 2-adrenoceptors on neural membranes isolated from various brain areas and upon the function of presynaptic alpha 2-adrenoceptors during field stimulation of hippocampal slices. Rats were injected with morphine every 8 h for 14 days with doses which started at 10 mg/kg per injection i.p., and which increased every 3 days to a final dose of 100 mg/kg per injection on the last 2 days. At 8 and 32 h after the last injection the Bmax for [3H]clonidine binding to neural membranes from various brain areas was significantly decreased. At the same times, the fractional release of [3H]noradrenaline during field stimulation of hippocampal slices was increased and the sensitivity of the hippocampal slice to clonidine was reduced which indicated the development of a functional subsensitivity of the presynaptic alpha 2-adrenoceptor. These changes in receptor function persisted at 72 h after the last morphine injection although at this time there were marked increases over control values in [3H]clonidine binding to membranes from all rat brain areas except the caudate nucleus. These findings suggest that changes in alpha 2-adrenoceptor number and function which develop during long-term morphine administration might play an important role in opiate dependence.

Animals↗

PubMed1989

Electrophysiological correlates of presynaptic alpha 2-receptor-mediated inhibition of norepinephrine release at locus coeruleus synapses in dentate gyrus.

Despite an abundance of evidence that presynaptic alpha 2-adrenergic receptors mediate inhibitory control of the release of norepinephrine (NE) from the terminals of locus coeruleus (LC) neurons, few studies have demonstrated the physiological significance of this "autoreceptor"-mediated inhibition on NE-mediated synaptic activity within the mammalian brain. This question was addressed by examining the effects of systemic administration of alpha 2-adrenergic agonists and antagonists on the ability of LC stimulation to augment the population spike recorded in the dentate gyrus in response to activation of the perforant path (PP). Extracellular field potentials were recorded in the cell body and dendritic layer of dentate gyrus following single shocks of the entorhinal cortex in halothane-anesthetized rats. Stimulation of the ipsilateral LC 35 msec prior to PP activation produced a short-term enhancement of the population spike amplitude recorded in the cell layer but did not significantly alter dendritic potentials. The effects of LC stimulation were blocked by administration of the beta-adrenergic antagonist propranolol but not the alpha 2-antagonist idazoxan and were abolished by pretreatment of animals with the catecholamine neurotoxin 6-hydroxydopamine. Administration of clonidine reversibly abolished the enhancement produced by LC conditioning. The effect of clonidine was dose dependent and was blocked by administration of idazoxan, which restored the LC potentiative effect. Conditioning stimulation of LC noradrenergic axons in the dorsal bundle also potentiated the PP-evoked population spike, and this effect was equally sensitive to the depressant action of clonidine. In comparison, clonidine, in the range of dosages tested, did not significantly affect the potentials evoked in the dendritic or cell layer by presentations of unconditioned PP test stimuli. We interpret these data to provide evidence for a functional impairment of LC-mediated physiological action on postsynaptic target cells as a result of presynaptic alpha 2-autoreceptor-mediated feedback inhibition of NE release.

Action Potentials↗

PubMed1988

New evidence for a gating action of norepinephrine in central neuronal circuits of mammalian brain.

Many previous studies have examined the effects of norepinephrine (NE) on neuronal responsiveness to synaptic inputs and putative transmitter substances and have described differential depressant actions of NE on stimulus evoked versus spontaneous discharge such that the "signal to noise" ratio of threshold responses was increased. In the present studies, similar experimental strategies employing a combination of microiontophoresis, single unit recording and afferent pathway stimulation in intact anesthetized and brain tissue slice preparations have revealed noradrenergic "gating" actions whereby weak or subthreshold synaptic stimuli can evoke threshold neuronal responses in the presence of iontophoretically applied NE or following electrical stimulation of the locus coeruleus. Overall, these results suggest that potentially threshold excitatory and inhibitory synaptic inputs may normally arrive at central neurons but appear weak or absent except during behavioral conditions favoring the synaptic release of NE. As such, these findings provide evidence that signal to noise ratio may not be the only potential modulatory action expressed by NE in noradrenergic target circuits of the mammalian brain.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1988

Electrophysiological evidence for alpha 1- and alpha 2-adrenoceptors in solitary tract nucleus.

The effects of microiontophoresis of norepinephrine and epinephrine were examined on the spontaneous neuronal activity of single neurons in the nucleus tractus solitarius (NTS) in urethan-anesthetized rats. Neuronal responses to catecholamine iontophoresis were examined in the absence and presence of the alpha 1-adrenergic antagonist, prazosin, and the alpha 2-antagonist, idazoxan, to characterize the subtypes of alpha-adrenergic receptors mediating catecholamine action in this important autonomic nucleus. Norepinephrine produced inhibitions in firing, which were blocked primarily by idazoxan, whereas epinephrine-induced neuronal inhibitions were blocked by either prazosin or idazoxan. Inhibitions of spontaneous firing were also produced by iontophoresis of methoxamine, an alpha 1-selective agonist, or the alpha 2-selective agonist clonidine in all neurons that were tested. Neuronal responses to methoxamine were blocked selectively by prazosin, whereas the effects of clonidine were antagonized selectively by idazoxan. These data provide evidence at the level of the single unit that catecholamines may affect activity in the NTS via interactions with both alpha 1- and alpha 2-adrenergic receptors.

Action Potentials↗

PubMed1987

Electrophysiological correlates of presynaptic opiate receptor activation: reduction in norepinephrine-mediated inhibition from the locus coeruleus.

Inhibitory responses of rat cerebellar Purkinje cells to locus coeruleus (LC) stimulation and iontophoresis of norepinephrine (NE) were examined before and after administration of morphine to determine whether the inhibitory modulation of NE release by opiates results in a functional impairment in noradrenergic synaptic action. Administration of morphine systemically (0.2-1.2 mg/kg, i.v.) or by iontophoresis reduced inhibitions in Purkinje firing elicited by LC stimulation without affecting depressions in activity induced by postsynaptic applications of NE. This antagonistic effect of morphine on LC-induced inhibition was reversed or prevented by naloxone and mimicked by administration of levorphanol but not dextrorphan. Morphine increased the excitatory response of Purkinje cells to monosynaptic input from the parallel fibers, whereas it blocked gamma-aminobutyric acid-induced inhibitions in firing via a non-opiate receptor-mediated mechanism. These results demonstrate that morphine interferes with synaptic inhibition derived from the LC and suggest that this may occur via activation of presynaptic opiate receptors residing on noradrenergic nerve terminals.

Animals↗

PubMed1987

Adrenergic responses of baroreceptive cells in the nucleus tractus solitarii of the rat: a microiontophoretic study.

Anatomical and pharmacological evidence suggests a role for catecholamines (CAs) in the modulation of the baroreceptor reflex within the nucleus tractus solitarii (NTS). Single neurons in the NTS of the rat were studied for their responses to activation of the baroreceptor reflex and to iontophoretic administration of dopamine, norepinephrine (NE), and epinephrine (EPI) to determine the relationship between the effects of baroreflex activation and CA application on baroreceptive neurons in the vagal sensory nucleus. Of 269 cells studied, 104 (38.7%) exhibited decreases and 41 cells (15.2%) showed increases in firing rate in response to baroreflex activation, while the remaining 124 neurons showed no response. All 3 CAs inhibited spike activity in the majority (68.5%) of NTS cells. These inhibitory effects on spontaneous firing were observed regardless of the response profile of a particular neuron to baroreflex activation. The inhibitory effects of NE and EPI on NTS neuronal activity were specifically blocked by the alpha-adrenergic receptor antagonist tolazoline, but not by the beta-adrenergic antagonist sotalol. These results indicate that CAs may interact at several sites within the NTS to influence baroreflex integration, and that the effects of NE and EPI on neuronal activity are mediated by an alpha-adrenergic receptor.

Action Potentials↗

PubMed1987

Changes in cortical beta-adrenergic receptor density and neuronal sensitivity to norepinephrine accompany morphine dependence and withdrawal.

Radioligand binding experiments were carried out in conjunction with electrophysiological recordings in vivo in the parietal cortex in rats to assess changes in postsynaptic beta-adrenergic receptor function that result after chronic administration of morphine and during morphine withdrawal. Chronic treatment of rats with morphine for 14 days resulted in a 38% increase in the density of beta-adrenergic receptors in the parietal cortex, as measured by the binding of the specific antagonist [3H]dihydroalprenolol (DHA). In comparison, following withdrawal in the chronic morphine-treated animals, the number of specific [3H]DHA binding sites in this same cortical region was decreased 25%, when compared to saline-treated controls. These alterations in cortical beta-adrenergic receptor density were not accompanied by a significant change in the dissociation constant (Kd) for [3H]DHA or in the inhibitory constants (Ki) for the specific agonists norepinephrine and isoproterenol. Microiontophoretic testing revealed that the changes in beta-adrenergic receptor density found in parietal cortex after chronic morphine treatment and during morphine withdrawal were accompanied by a selective increase and decrease, respectively, in the sensitivity of cerebrocortical neurons in the same region to beta-adrenergic stimulation. These results suggest that changes in central adrenergic function might be related to the formation and/or expression of dependence on morphine.

Animals↗

PubMed1986

Interaction of serotonin with somatosensory cortical neuronal responses to afferent synaptic inputs and putative neurotransmitters.

The present study was conducted to investigate the action of serotonin (5-HT) on synaptic transmission within local circuits of the rat somatosensory cortex. Responses of single somatosensory cortical neurons to activation of excitatory and inhibitory synaptic pathways or iontophoretic application of putative neurotransmitters were examined before, during and after microiontophoresis of 5-HT. Monoamine-induced changes in neuronal responsiveness were quantitatively assessed by computer-based analysis of peri-event histograms. 5-HT typically exerted a differential inhibitory effect on neuronal firing, such that stimulus-induced responses were reduced relative to spontaneous discharge. In 16 of 24 (67%) of the cells tested, 5-HT depressed synaptically evoked excitation more than background firing such that "signal to noise" ratio was decreased. In some cases evoked spiking was reduced from control levels at doses of 5-HT subthreshold for producing direct depression of baseline firing rate. Cortical neuron excitatory responses to iontophoretically applied acetylcholine (8 of 13 cells) and glutamate (10 of 15 cells) were also reduced during microiontophoresis of 5-HT. A similar reduction in inhibitory efficacy was observed in 62% of the cases (10 of 16 cells) where 5-HT was interacted with GABA-induced depressant responses. Local administration of 5-HT also resulted in an antagonism of stimulus bound inhibition of firing (9 of 11 cells). These results are contrasted with previously observed facilitory effects of norepinephrine (NE) on cortical neuronal responsiveness to afferent synaptic inputs and putative transmitter agents. It is suggested that endogenously released 5-HT and NE may exert complementary modulatory-type actions on neuronal responsiveness as a means of regulating the transfer of sensory information through local cerebrocortical circuits.

Acetylcholine↗

PubMed1986

Presynaptic alpha 2 adrenoreceptor function in dependent rats before and after morphine withdrawal.

Changes in the number of alpha 2 adrenoreceptors in the hippocampus, as measured by the specific binding of 3H-clonidine, were compared to changes in presynaptic alpha 2 adrenoreceptor function in electrically stimulated hippocampal slices. In dependent rats the specific binding of 3H-clonidine was reduced significantly. At 32 h after withdrawal binding began to return toward normal values, and at 72 h after withdrawal was significantly greater than that seen in saline-treated rats. In hippocampal slice experiments sensitivity to clonidine was significantly decreased in morphine-dependent animals and returned toward normal values after withdrawal. At 72 h after withdrawal, the sensitivity to clonidine of the presynaptic alpha 2 adrenoreceptor remained depressed although receptor density as measured in the binding studies was increased. This study suggests that the changes in the function of presynaptic alpha 2 adrenoreceptors might be important in the development of dependence upon morphine.

Animals↗