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A Ettenberg

Publications and source records attributed to A Ettenberg.

At least 55 records · Page 3Linked to original sources
PubMed1986

Comparison of circling induced by unilateral intrastriatal microinjections of haloperidol, clozapine and CCK-8 in rats.

The existence of the neuropeptide cholecystokinin (CCK) within a subpopulation of central dopamine (DA) neurons has led to speculations that the peptide may serve as an endogenous modulator of DA functions. To test this possibility, the present study examined the pharmacological action of CCK-8 by comparing its effects on DA-mediated circling behavior with those of a typical (haloperidol; HAL) and an atypical (clozapine; CLZ) dopamine antagonist neuroleptic drug. Rats received unilateral intrastriatal infusions of either sulfated CCK-8 (1, 2, or 8 micrograms), HAL (5 micrograms) or CLZ (5 or 20 micrograms) 15 minutes after systemic injection of d-amphetamine (1 mg/kg). Animals were then placed into rotational chambers where the number and direction of complete 360 degree turns was automatically recorded over a 1 hour session. HAL produced strong and almost exclusive ipsilateral circling while the responses after CLZ and CCK-8 were reliably more variable in rotational direction. More specifically, the results suggest that CLZ is only a weak antagonist of behaviors mediated by striatal DA activation while CCK seems to be devoid of antidopaminergic properties in the striatum.

Animals↗
PubMed1986

Subcutaneous administration of behaviorally effective doses of arginine vasopressin change brain AVP content only in median eminence.

The accumulation of [8-arginine]vasopressin (AVP) in brain areas inside the blood-brain barrier (thalamus-hypothalamus, amygdala with overlying temporal cortex, hippocampus and cerebral cortex) and outside the blood-brain barrier (median eminence of the hypothalamus and area postrema) was measured after subcutaneous injection of the hormone. The plasma concentrations of AVP peaked at 5 min after subcutaneous injection and declined in a biphasic manner over the next 115 min. The concentration of AVP in brain tissue samples peaked at 20 min after the subcutaneous injection of AVP; the decline of AVP in the areas protected by the blood-brain barrier followed the time course seen for plasma. The concentration of AVP in the brain areas not so protected also peaked at 20 min but these declined at rates that differed from other brain areas and plasma. The concentration of AVP in the plasma and in most brain areas depended on the dose administered, while those in the median eminence and in the area postrema did not. Water deprivation for 24 and 48 h significantly elevated both the plasma AVP concentration and the concentration of AVP in the hypothalamus and in the amygdala-temporal cortex samples. The increases in AVP after water deprivation are limited to these two regions and are quantitatively much lower than after peripheral administration. Furthermore, when the brains of anesthetized rats were perfused free of blood, there were no changes in regional brain AVP content after subcutaneous treatment with 5,000 ng/kg of AVP, except for the median eminence. These data suggest that circulating AVP does not enter the parenchyma of brain areas protected by the blood-brain barrier in sufficient quantities to be detected by our assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Neuroleptic-induced deficits in operant responding for temperature reinforcement.

The hypothesis that neuroleptic drugs interfere with operant behaviors by attenuating the rewarding properties of positive reinforcers, was examined in rats trained to lever-press for external heat in a cold environment. Unlike traditional reinforcers, such as food and water, reducing the reward magnitude of heat (by reducing the intensity or duration of the stimulus) results in compensatory increases in operant responding. Neuroleptic pretreatment (0.1, 0.2, 0,4 mg/kg of alpha-flupenthixol) produced only dose-dependent decreases in responding thereby interfering with the animals' ability to behaviorally maintain their internal core temperature. In a temperature-gradient test paradigm (requiring less physical effort on the part of the subjects) alpha-flupenthixol did not alter the animals' preferred environmental temperature, nor did it disrupt behavioral thermoregulatory ability. These data suggest that at least part of the behavioral deficit observed during neuroleptic treatment is due to a disruption in the performance capabilities of the subjects.

Animals↗
PubMed1985

Effects of peripherally injected vasopressin and des-glycinamide vasopressin on the extinction of a spatial learning task in rats.

An elevated eight-arm radial maze was employed to study the effects of neuropeptide administration on the spatial learning abilities of food-deprived rats. Following 18 days of reinforced training, each animal was briefly exposed to the maze with no food available in any of the eight food-cups. Immediately after this preliminary trial, animals were injected with a single subcutaneous dose of either saline, arginine vasopressin (AVP: 1.0 or 5.0 micrograms/kg), or an AVP analog with only weak endocrinological activity, des-gly-arginine vasopressin (DG-AVP: 1.0, 5.0 or 10.0 micrograms/kg). Additional extinction trials were conducted at 2, 4, 6 and 8 h post-injection. These tests consisted of individually placing an animal on the empty maze and recording the number of arms chosen in a 5-min period. In this situation, animals learn that food is no longer present in the maze and, consequently, extinguish responding. Vasopressin potentiated this radial maze extinction behavior while DG-AVP produced behavioral results directionally opposite to those predicted by a memory facilitation hypothesis. In a subsequent experiment, vasopressin had no effects on unconditioned locomotor activity measured 2 and 4 h post-injection. These results suggest that: vasopressin improved the learning that occurred during extinction of conditioned appetitive behaviors, these vasopressin effects on conditioned behavior were independent of any unconditioned, sedative or non-specific actions of the peptide, and peripheral endocrinological responses may be necessary to demonstrate memory-enhancing effects following peripherally administered AVP.

Animals↗
PubMed1984

Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats.

The hypothesis that separate neural systems mediate the reinforcing properties of opioid and psychomotor stimulant drugs was tested by examining the role of mesolimbic dopamine (DA) neurons in maintaining intravenous heroin and cocaine self-administration. After local destruction of the DA terminals in the nucleus accumbens (NAcc) with 6-hydroxydopamine (6-OHDA), rats trained to self-administer cocaine and heroin on alternate days were observed for changes in their drug-seeking behaviors. Postlesion responding for cocaine showed a time-dependent decrease or extinction, whereas heroin self-administration showed a time-dependent recovery. By the fifth trial postlesion, heroin self-administration had recovered to 76% of prelesion baseline levels, but cocaine self-administration had dropped to 30% of prelesion baseline rates. Thus, selective lesions of the DA terminals in the nucleus accumbens significantly attenuate cocaine but not heroin self-administration. These data support the hypothesis that independent neural substrates are responsible for the reinforcing actions of these two drugs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Different effects of cholecystokinin and satiety on lateral hypothalamic self-stimulation.

The effects of cholecystokinin (CCK) and satiety were compared in animals lever-pressing for rewarding electrical stimulation of the lateral hypothalamus. For some rats, conditions of food deprivation and satiation, respectively, increased or decreased responding whereas the self-stimulation behavior of other rats was unresponsive to these feeding manipulations. CCK, at doses thought to signal satiety, reduced the responding of all rats independent of whether they were, or were not, responsive to real satiety. This same result was obtained with the aversive agent lithium chloride. These data suggest that the reduced feeding observed following CCK administration is due to aversive consequences and not satiety.

Analysis of Variance↗
PubMed1984

Intracerebroventricular application of a vasopressin antagonist peptide prevents the behavioral actions of vasopressin.

Three experiments were conducted to test the hypothesis that the memory-improving properties of peripherally-applied vasopressin (AVP) were related to its aversive (i.e. arousing) actions. The memory effects of AVP were observed in a one-trial food-finding task where non-deprived rats were briefly exposed to a large open field that contained an alcove in which a high-incentive familiar food reward (sweetened milk) was freely available. AVP injections immediately upon removal from the open-field produced faster latencies to refind the alcove (compared to vehicle controls) when tested 48 h later. The aversive actions of AVP were demonstrated in two behavioral assays: (1) a conditioned taste aversion test in which rats learned to avoid a preferred saccharin solution after it had been paired with injections of AVP; and (2) a conditioned place test in which rats learned to avoid a distinctive environment associated with AVP administration. Both the memory and aversive responses to AVP were prevented, in a dose-dependent manner, by immediate pretreatment with intracerebroventricular infusions of the pressor antagonist analog 1-deaminopenicillamine-2-(O-methyl)-tyrosine AVP. The large antagonist doses required to block AVP's behavioral effects suggest that the critical site of action may be far removed from the lateral ventricles. The possibility that AVP-induced improvements in memory result from peripheral arousing actions is discussed.

Animals↗
PubMed1984

Behavioral effects of peripheral administration of arginine vasopressin: a review of our search for a mode of action and a hypothesis.

In this review we present data summarizing our studies concerning the mechanism of action for the behavioral effects of peripheral arginine vasopressin (AVP) administration. We have demonstrated a clear performance improvement in a one trial appetitive task designed to measure the memory-learning process. This behavioral effect is blocked by peptide analogs which block the pressor response to AVP. From these data, and from other data obtained in aversively motivated tasks, we hypothesize that peripheral AVP injections induce effects of physiological-endocrinological origin and that these peripheral signals (e.g. vasopressor actions) alert and arouse the animal, thus helping to improve its association of environmental events. This hypothesis is similar to that proposed by others regarding peripheral hormones and memory and still leaves open the possibility that vasopressin in the brain acts independently of the above proposed action for peripherally derived vasopressin.

Animals↗
PubMed1984

Effects of opiate antagonists and their quaternary derivatives on heroin self-administration in the rat.

Quaternary derivatives of naloxone and naltrexone, methyl naloxonium chloride(ORG 10908) and naltrexone methobromide ( MRZ 2663BR ), respectively, were compared with the parent compounds for their ability to antagonize the reinforcing properties of heroin as measured in an operant, i.v., self-administration paradigm. As expected, lower doses (up to 0.2 mg/kg) of naloxone and naltrexone produced dose-dependent increases in heroin self-administration, but at higher doses (10-30 mg/kg) these drugs produced transient decreases (20-100 min) in self-administration followed by recovery. Naltrexone was approximately 1.5 times more potent than naloxone in increasing heroin self-administration at the lower doses (up to 0.2 mg/kg) and had a slightly longer duration of action. The quaternary derivatives were ineffective as antagonists of heroin self-administration in doses 200 times greater than the effective antagonist dose of naloxone or naltrexone. These results support the hypothesis that the acute reinforcing properties of i.v. opiates associated with the sensation of the "rush" involve opiate receptors located within the central nervous system and do not involve peripheral opiate receptors.

Animals↗
PubMed1983

Chemical and physiological aspects of the actions of lithium and antidepressant drugs.

The possible mechanisms underlying the anti-manic actions of lithium have been examined in a variety of interdisciplinary experiments. The possibility that lithium can regulate the sensitivity changes in dopaminergic transmission produced by chronic treatment with haloperidol has been tested. Although a modest modification of behavioral responses to the dopamine agonist apomorphine was found, there was no evidence that this action of lithium reflected alterations of the binding parameters of dopamine-related ligands. In other studies, consistent, dose-dependent increases in brain enkephalin content were found after rats consumed a specially manufactured lithium diet for 2-3 weeks. Not only were brain enkephalin levels increased after this treatment, but some signs of basal analgesic responsiveness also suggested that the elevated levels of enkephalins were functionally significant. To test the possibility that the effects of lithium may not be seen in normal rats, the effects of lithium were compared on spontaneously hypertensive and unaffected, normotensive rats of a related strain. Treatment with lithium altered blood pressure in the hypertensive strain but did not affect blood pressure in the controls. These studies suggest that multiple brain systems may be regulated by treatment with lithium but that the critical pathophysiological process may not be demonstrable in the normal rat.

Animals↗
PubMed1983

Vasopressin potentiation in the performance of a learned appetitive task: reversal by a pressor antagonist analog of vasopressin.

Rats were tested in a simple one-trial water-finding task for the effects of arginine vasopressin (AVP) on performance of an appetitive task. On the training day, each animal was exposed for 5 min to a novel open-field environment that contained a water-tube located in an alcove set into one of the walls of the enclosure. Immediately upon removal from the enclosure, the animals received a subcutaneous injection of either AVP (1 microgram/rat) or vehicle solution. When water-deprived and tested 48 hr later, vasopressin-treated rats found the water tube reliably faster than controls. In other groups of animals, this potentiation in learned performance was prevented by concurrently treating the rats with a vasopressin analog having potent pressor antagonist properties. These results are consistent with the notion that vasopressin may play a role in memory consolidation, but peripheral visceral factors may mediate this action.

Animals↗
PubMed1983

Can aversive properties of (peripherally-injected) vasopressin account for its putative role in memory?

Rats injected with arginine vasopressin (AVP) immediately after exposure to a novel open-field environment found a water tube faster than saline injected rats, when water-deprived 48 h later. Other experiments demonstrated that this effect did not result from some conditioned or pharmacologically-induced hyperactivity in the experimental group. Although these results are consistent with a role for AVP in 'memory' mechanisms, lithium chloride, a known illness-producing agent, produced a reduction in latency to find the water tube identical to that of AVP. In separate experiments, AVP acted as an effective unconditioned stimulus in conditioned taste and place aversion studies. AVP also produced a dose-dependent disruption of spontaneous locomotor activity. Together, these data indicate that peripheral AVP administration has aversive consequences. Desglycinamide arginine vasopressin (an AVP analog with weak pressor-agonist properties) produced no observable aversive effects and did not improve test performance in the appetitive water-finding task. It is suggested that the apparent memory-enhancing properties of peripherally administered AVP, at least in appetitive test paradigms, may depend on its aversive and consequently arousing actions.

Animals↗
PubMed1982

Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems.

The hypothesis that separate neural systems mediate the reinforcing properties of opiate and psychomotor stimulant drugs was tested in rats trained to lever-press of IV injections of either cocaine or heroin during daily 3-h sessions. Pretreatment with the opiate receptor antagonist drug naltrexone produced dose-dependent increases in heroin self-administration, but had no effect on the rate or pattern of cocaine self-administration. Similarly, pretreatment with low doses of the dopamine antagonist drug alpha-flupenthixol produced dose-dependent increases in cocaine but not heroin self-administration. High doses of alpha-flupenthixol eliminated all responding for cocaine and slightly reduced heroin self-administration. The specificity with which the two antagonist drugs exerted their behavioral effects strongly suggests that independent neural substrates are responsible for the reinforcing actions of heroin and cocaine.

Animals↗
PubMed1981

Response artifact in the measurement of neuroleptic-induced anhedonia.

Systemic administration of the neuroleptic drug alpha-flupenthixol attenuated lever-pressing behavior in rats responding for rewarding brain stimulation. The magnitude of this attenuation was dose-dependent and resembled the effects of reward reduction and termination. However, when the operant response requirements of the same rats were changed to nose poking, identical drug treatments produced relatively little attenuation in performance. These data do not support the belief that neuroleptics produce a general state of anhedonia. Rather, the apparent suppression of reinforced behaviors depends at least in part on the kinetic requirements of the response.

Animals↗
PubMed1981

Pimozide attenuates conditioned taste preferences induced by self-stimulation in rats.

Conditioned taste preferences (CTPs) were observed in rats who drank flavored water followed by a session of self-stimulation. Control groups that did not self-stimulate did not exhibit CTPs. Other taste/SS pairings conducted under the influence of the dopamine receptor antagonist pimozide (0.1 or 0.3 mg/kg, IP) resulted in dose-dependent reduction in the size of the CTPs. No evidence of any aversive effects (conditioned taste aversions) of the pimozide treatment were observed in the no-stimulation control groups. These data suggest that, in addition to its effects on responding, low doses of pimozide reduce the rewarding properties of self-stimulation.

Animals↗