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A L Beckman

Publications and source records attributed to A L Beckman.

At least 37 records · Page 2Linked to original sources

In vivo analysis of dopamine and its metabolites in the caudate nucleus during euthermia and hibernation.

Golden-mantled ground squirrels (Citellus lateralis) were chronically implanted with a unilateral push-pull cannula in the caudate nucleus. Perfusates obtained in these unanesthetized, unrestrained animals during the euthermic (non-hibernating) and hibernating states were analyzed for dopamine (DA) and its metabolites (homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxy-4-hydroxyphenethanol (MOPET) using high performance liquid chromatography with electrochemical detection. The data revealed clear differences in the performance of the caudate DA system in the two states. During the euthermic state, DA metabolism was indicative of a constant and high turnover rate. Free DA was not detectable in the majority of samples, HVA was detected at consistently high levels, and DOPAC and conjugated DA were present at low levels. By contrast, DA metabolism was sharply altered during hibernation. Free DA was present at high concentrations and HVA concentrations were low. DOPAC was not detected in any sample whereas MOPET was present in all samples. Conjugated DA was present at high concentrations during the second half of the hibernation bout. The shift in the post-release disposition of DA could enhance the stability of DA receptors (i.e. prevent supersensitivity) during the prolonged periods of reduced neural activity typical of hibernation.

3,4-Dihydroxyphenylacetic Acid↗

Antagonism of brain opioid peptide action reduces hibernation bout duration.

The effect of continuous intracerebroventricular (i.c.v.) administration of naloxone on the duration of individual bouts of hibernation was investigated in the golden-mantled ground squirrel (Citellus lateralis). Following entrance into hibernation, naloxone was continuously administered by an osmotic minipump at a rate of 1 microliter/h through a chronically implanted unilateral i.c.v. cannula guide. Naloxone (1, 5 and 7.5 micrograms/microliter) produced a dose-dependent reduction in hibernation bout duration ranging from 1 to 4 days (13.9-62.3% of expected bout duration). These data suggest that selected endogenous opioid system neurons may contribute to the CNS maintenance of the hibernating state and, consequently, to the overall conservation of energy in this species.

Animals↗

Differential effect of environmental temperature on morphine physical dependence and abstinence.

1) Ambient temperature (Ta) significantly influenced the display of 4 of the 14 naloxone-precipitated withdrawal signs (nesting, flat posture, vocalization, dyspnea) in morphine-dependent, non-hibernating ground squirrels (Citellus lateralis). 2) Analysis of variance performed on the six quantified signs revealed that Ta during withdrawal, but not during the development of physical dependence, was a significant factor in determining the expression of two signs (nesting and vocalization). 3) The interaction between the influence of Ta during the periods of morphine administration and abstinence was a significant factor in determining the expression of nesting behavior, a finding that is consistent with the natural role of nesting as a behavioral thermoregulatory response. 4) We conclude that environmental temperature modulates the expression of selected components of the naloxone-precipitated abstinence syndrome in C. lateralis without exerting a measurable influence on the development of morphine physical dependence itself.

Animals↗

Effects of iontophoretically applied (+)- and (-)-naloxone on rat hypothalamic and septal neurons.

The purpose of this study was to investigate the possible independent actions of both (+)-and (-)-naloxone on individual neurons in the preoptic/anterior hypothalamus (POAH) and septal area (SA) of the rat brain. Morphine and (-)-naloxone were applied to 31 neurons in the SA (n = 11) and the POAH (n = 20). Morphine depressed the spontaneous activity in 19 of 31 neurons. (-)-Naloxone at currents less than 10 nA did not influence these neurons. However, (-)-naloxone applied in excess of 10 nA reduced spontaneous activity in 28 of 29 neurons. This effect of (-)-naloxone was stereospecific; (+)-naloxone did not alter the spontaneous rate in 12 of 14 cells when alternately applied with (-)-naloxone at the same current intensity. Application of (+)- and (-)-naloxone at supramaximal currents produced a diminution of spike amplitude and an increase in the duration of the action potential. The results of this study indicate that naloxone reduces spontaneous activity via two mechanisms. One involves a direct stereospecific action, and a second produces a non-specific reduction in spike amplitude and a prolongation of spike duration.

Action Potentials↗

Seasonal variation of morphine physical dependence.

The characteristics of morphine physical dependence in ground squirrels (Citellus lateralis) were examined during each of the four annual seasons. The results showed that this rodent hibernator exhibits a strong and characteristic naloxone-precipitated abstinence syndrome during its non-hibernation state, irrespective of the season. Although qualitatively unchanged throughout the year, the abstinence syndrome showed clear quantitative seasonal differences. These differences were evident in terms of both the number of occurrences of particular signs and the percentage of the morphine-dependent population exhibiting them.

Animals↗

Seasonal variation in thyrotropin-releasing hormone (TRH) content of different brain regions and the pineal in the mammalian hibernator, Citellus lateralis.

We have measured the endogenous TRH concentration in the pineal and 9 brain regions of a seasonal hibernator, the golden-mantled ground squirrel, during euthermia and hibernation in order to investigate the possibility that changes in TRH concentration might occur in association with naturally-occurring changes in CNS-mediated physiological and behavioral processes. Regional TRH content was assessed by radioimmunoassay in adult animals that were killed during euthermia in the mid-portion of each season and during hibernation in mid-winter. No significant changes in TRH concentration related to season or to hibernation versus euthermic state were noted in the hippocampus, brainstem, or cerebellum. In the olfactory bulb, preoptic area, and pineal, seasonal variation within euthermic groups was evident. During hibernation, statistically significant decreases in TRH content occurred in the forebrain, olfactory bulb, hypothalamus, septum, preoptic area, and midbrain. Significant fluctuations during hibernation were also observed in the pineal. In this structure, TRH concentration varied in relation to the phase of the hibernation bout. TRH content in the last quarter of the bout was three times greater when compared to values observed in the first quarter of the bout. These results suggest that TRH may be involved in the control processes attributed to these regions and support a role for TRH in the neural control of hibernation.

Animals↗

Physical dependence on morphine fails to develop during the hibernating state.

Physical dependence on morphine occurs in a typical fashion during the active state of the mammalian hibernator Citellus lateralis, but does not occur when morphine exposure is confined to the hibernating state. Morphine exposure during hibernation can produce stereotyped behavior, thus demonstrating partial responsiveness of the central nervous system to opioids during this natural state.

Animals↗

Effects of thyrotropin releasing hormone on hypothalamic thermosensitive neurons of the rat.

The actions of thyrotropin releasing hormone (TRH) were tested on the firing rat of temperature-sensitive and temperature-insensitive neurons in the rat preoptic/anterior area of the hypothalamus (POA). Iontophoretic application of TRH resulted in inhibition of the firing rate of temperature-insensitive, warm-sensitive and cold-sensitive neurons. The inhibitory response of cold sensitive neurons in TRH was relatively mild, however, and 2 of 6 of these neurons inhibited by TRH also displayed rebound increases in discharge rate following cessation of TRH application. These results parallel the hyperthermic effects of microinjected TRH and lend further support of the hypothesis that TRH acts as a neurotransmitter or neuromodulator in the POA portion of the CNS thermoregulatory network.

Animals↗

Characterization of midbrain component of the trigger for arousal from hibernation.

The ability of the midbrain reticular formation (MRF) to trigger arousal from hibernation and to change body temperature (Tb) during euthermia was tested in golden-mantled ground squirrels (Citellus lateralis). During hibernation (ambient temperature 5-6 degrees C) microinjections of cholinomimetic compounds (acetylcholine and carbachol) triggered full arousal or produced transient increases in Tb in 15 out of 19 tests; MRF microinjections of norepinephrine (NE) and 5-hydroxytryptamine (5-HT), at the same concentrations that produced full arousal when microinjected into the preoptic/anterior hypothalamus (PO/AH) area in previous experiments, has no effect on Tb in 13 out of 16 tests. In experiments on euthermic ground squirrels tested at an ambient temperature of 25 degrees C, MRF microinjections of acetylcholine raised Tb, whereas the monoamines had no significant effects. These results show that cholinoceptive neurons in the MRF can trigger arousal from hibernation and increase Tb during euthermia. The failure of NE and 5-HT to produce any significant effects at the same doses that were reported to be effective in the PO/AH indicates that the functional organization of the MRF portion of the arousal mechanism is different from that reported for the PO/AH.

Acetylcholine↗

Inhibition of the CNA trigger process for arousal from hibernation.

Ground squirrels (Citellus lateralis) produced three distinct types of thermogenic response during hibernation. These responses were evoked spontaneously as well as after stimulation produced by brief handling, or after microinjection of acetylcholine into the midbrain reticular formation. Type I responses were characterized by small magnitude and a slow (mean rate, 0.03 degrees C/min), variable rising phase. Type II responses were characterized by a smooth, rapid rising phase with a mean rate of increase of 0.11 degrees C/min and by an abrupt reversal of the rising phase within a restricted ceiling temperature band with a mean value of 9.4 degrees C. The third type of response, full arousal, was characterized by a return of body temperature to euthermic (nonhibernating) levels and by an early rising phase that was indistinguishable from the rising phase of type II responses. This indicates that the rising phase of type II responses and the duplicate portion of full arousals are produced by a common neuronal mechanism that functions as the trigger for arousal from hibernation, and that this mechanism can be spontaneously inhibited when increasing internal temperature reaches a hibernation ceiling level.

Acetylcholine↗

Changes in CNS responsiveness during hibernation.

The ability of the midbrain reticular formation (MRF) to produce thermogenic responses and to trigger arousal from hibernation was tested during successive quarters of individual hibernation bouts. Golden-mantled ground squirrels (Citellus lateralis) were implanted with bilateral cannula guides into the MRF. Single, bilateral, 1-mul injections of acetylcholine (ACh) at concentrations of 50, 100, or 200 mug/mul were delivered in each quarter of the same bout or in selected quarters of different bouts. The results show that the magnitude of thermogenic responses evoked by ACh stimulation of the MRF was depressed during the early portion of the bout and increased as time in the bout elapsed. Furthermore, the magnitude of responses evoked during hibernation was depressed in comparison to those evoked during euthermia, indicating the influence of inhibition on the responsiveness of the CNS during hibernation. We suggest that during hibernation, a progressive change in responsiveness of the CNS, perhpas focused in the MRF, controls the duration of each hibernation bout.

Acetylcholine↗