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A Ettenberg

Publications and source records attributed to A Ettenberg.

At least 37 records · Page 2Linked to original sources
PubMed1993

Qualitative and quantitative differences in the operant runway behavior of rats working for cocaine and heroin reinforcement.

Animals were trained to traverse a straight alley for drug reinforcement consisting of five IV injections of either 0.75 mg/kg/injection cocaine (n = 6) or 0.06 mg/kg/injection heroin (n = 6). Testing involved single daily trials during which the latency to leave the start box and the time required to traverse the alley were recorded for each animal. In addition, input from 12 pairs of infrared photocell detector/emittors placed along the length of the alley provided information on the precise location of the animal at 0.1-s intervals throughout the course of each trial. This information was recorded by computer and provided the basis for construction of graphic representations of each trial in the form of spatiotemporal records that revealed the precise route the subject took in getting to the goal box. The experiment revealed substantial differences in the runway behavior of heroin and cocaine animals. While the heroin group exhibited typical patterns of operant performance in that both start latency and goal times decreased gradually over the course of the experiment, cocaine animals were reliably slower than heroin subjects to leave the start box and exhibited a progressive increase in goal times over trials. The latter effect appeared to be a consequence of a "stop and retreat" behavior that was observed in all six cocaine subjects and increased in frequency as the experiment progressed. Because the runway behaviors exhibited here were emitted prior to delivery of the drug reinforcer, they suggest that the motivational state underlying drug-seeking behavior is qualitatively different for heroin- and cocaine-reinforced animals.

Animals↗
PubMed1993

Dopamine receptor blockade and reductions in thirst produce differential effects on drinking behavior.

The present study examined whether thirsty rats pretreated with the dopamine receptor blocker, pimozide, would show patterns of unconditioned drinking behavior similar to those produced by reductions in water deprivation. An examination of the drinking behavior of 23-, 16-, 12-, 4-, and 0-h water-deprived animals showed that reductions in thirst produced increased latencies to initiate drinking, changes in the within-session pattern of licking, and reductions in the total number of licks emitted. In contrast, administration of pimozide to 23-h deprived rats produced no effect on either initiation latencies or lick patterns, and only marginally reduced the total number of licks emitted during the session. Finally, pimozide produced no effect on either individual lick durations or interlick intervals. These results suggest that the primary motivational (i.e., "thirst") mechanisms and motoric processes underlying drinking behavior are relatively invulnerable to pimozide challenge.

Animals↗
PubMed1992

Pimozide prevents the development of conditioned place preferences induced by rewarding locus coeruleus stimulation.

Electrical stimulation in the vicinity of the cell bodies of the locus coeruleus (LC) has been shown to support self-stimulation behaviors in rats. In the present study, a Conditioned Place Test, sensitive to both rewarding and aversive qualities of brain stimulation, was employed to determine (a) whether rewarding locus coeruleus stimulation would result in place preferences and (b) if so, whether dopamine receptor antagonism would affect the development of such place preferences. Animals were pretreated with pimozide (0.0, 0.5 or 1.0 mg/kg) prior to exposure to two distinctive environments only one of which was paired with locus coeruleus stimulation. Rats that received vehicle injections prior to stimulation/place pairings developed strong preferences for the stimulation-paired environment while those animals pretreated with 0.5 mg/kg pimozide showed no reliable shift in preference from baseline performance. Additionally, animals injected with the 1.0 mg/kg dose of pimozide exhibited mild place aversions to the stimulation-paired environment. It is hypothesized that dopamine neurotransmission is important for the rewarding effects of locus coeruleus stimulation without which such stimulation appears to be aversive.

Animals↗
PubMed1992

Opposite effects of prefrontal cortex and nucleus accumbens infusions of flupenthixol on stimulant-induced locomotion and brain stimulation reward.

Ventral tegmental area (VTA) stimulation produced conditioned place preferences for stimulation-paired environments the magnitudes of which were dose-dependently reduced by systemic application of the dopamine antagonist, haloperidol (0.0, 0.15, 0.3 mg/kg). Bilateral microinjections of cis-flupenthixol (FLU) into the nucleus accumbens (0.0, 1.0, 5.0 or 10.0 micrograms) also resulted in reductions in the size of stimulation-induced place preferences as well as reductions in the magnitude of the hyperlocomotor response to 1.5 mg/kg (s.c.) D-amphetamine. Comparable microinjections of FLU into the medial prefrontal cortex (PFC) produced diametrically opposite effects: the size of VTA stimulation-induced place preferences was either unaffected (1.0 and 5.0 microgram groups) or slightly increased (10 micrograms group) and amphetamine-stimulated hyperlocomotion was dose-dependently potentiated. These behavioral findings suggest a dopamine-mediated modulatory role for the PFC over reward relevant elements within the nucleus accumbens.

Animals↗
PubMed1991

Different patterns of behavior produced by haloperidol, pentobarbital, and dantrolene in tests of unconditioned locomotion and operant responding.

Three motor-impairing drugs with different putative mechanisms of action (haloperidol 0.00, 0.075, 0.15, 0.30 mg/kg IP; pentobarbital 0.00, 4.5, 9, 12 mg/kg IP; and dantrolene 0.00, 5, 7.5, 10 mg/kg IP) produced strikingly similar patterns of dose-dependent attenuation in unconditioned locomotor behavior. However, the same drugs and doses produced highly divergent patterns of disruption when tested using different groups of rats in a food-rewarded operant task, which included both response initiation and maintenance components (FR1-FR1 two lever chain). Haloperidol animals began the session as fast as vehicle animals and slowed dose-dependently across trials; pentobarbital animals started off significantly slower than controls but soon achieved comparable speeds; and dantrolene animals were slower throughout the session. These results suggest that the observed neuroleptic-induced deterioration in responding over trials, especially in response initiation, was not simply a result of motoric disruption. Rather, the profile of this deterioration is consistent with the anhedonia hypothesis of neuroleptic action and supports the view that dopamine neurons are involved in the biological basis of food reward.

Animals↗
PubMed1991

Animal model for investigating the anxiogenic effects of self-administered cocaine.

Male albino rats were trained to traverse a straight alley for a reward of five intravenous injections of cocaine (0.75 mg/kg/injection in a volume of 0.1 ml/injection delivered over 4 s). Animals were tested one trial per day with the following dependent measures assessed on each trial: start latency, running time, the number of retreats, and the location within the alley where each retreat occurred. While start latencies remained short and stable, running times tended to increase over days. This effect was apparently related to a concomitant increase in the number of retreats occurring in the alley (r = 0.896). Retreats tended to occur in very close proximity to the goal box, suggesting that animals working for IV cocaine come to exhibit a form of conflict behavior (i.e., retreats) putatively stemming from the drug's well documented rewarding and anxiogenic properties. Consistent with this hypothesis was the demonstration that diazepam (0.5, 1.0, 2.0 mg/kg IP) pretreatment dose-dependently reduced the incidence of retreat behaviors in the alley. In addition, the rewarding efficacy of the cocaine dosing parameters was subsequently confirmed in the runway subjects by conditioned place preference. The present paradigm, therefore, provides a useful method for investigating the anxiogenic effects of self-administered cocaine in laboratory animals.

Animals↗
PubMed1991

Haloperidol attenuates conditioned place preferences produced by electrical stimulation of the medial prefrontal cortex.

A Conditioned Place Preference test procedure [Ettenberg and Duvauchelle (13)] was used to investigate the effects of dopamine antagonist challenge on the rewarding properties of medial prefrontal cortex (MPFC) electrical stimulation. Rats exhibited strong preferences for the side of a two-compartment test apparatus in which they experienced sessions of experimenter-administered 0.5-s trains of MPFC sine-wave 60-Hz stimulation. Pretreatment with the neuroleptic dopamine antagonist drug, haloperidol (0.0, 0.15, or 0.3 mg/kg IP), resulted in a dose-dependent reduction in the magnitude of observed place preferences. Preference tests were conducted 24 hours after drug-conditioning trials and, hence, were not subject to motoric or other nonspecific actions of the neuroleptic treatments. In a control experiment, haloperidol did not block the place aversions produced by dorsomedial tegmental stimulation. Animals can, therefore, recall place-associations formed in the presence of haloperidol, a result which challenges "state-dependent learning" explanations of the drug's actions. Together, these results are consistent with the view that dopamine neurotransmission is involved in the rewarding consequences of electrical stimulation in the medial prefrontal cortex.

Animals↗
PubMed1991

Conditioned incentive properties of a food-paired conditioned stimulus remain intact during dopamine receptor blockade.

Hungary rats were exposed to a conditioned stimulus (CS) event (either light onset or offset) before food delivery. After several weeks of contingent CS+/food pairings, animals were pretreated with either 0, 0.5, 0.75, or 1.0 mg/kg pimozide and exposed to the CS+ alone. Both vehicle- and neuroleptic-treated rats showed large elevations in locomotor activity immediately after CS+ presentation, in relation to pre-CS+ activity levels. This elevation in activity was apparently due to the conditioned motivational properties of the stimulus because animals that had previously received unpaired presentations of the CS and food failed to show similar responsiveness to the CS. Although pimozide did not affect responsiveness to the CS+, the neuroleptic did produce an overall suppression of locomotor activity during both pre- and post-CS+ periods. The results suggest that neuroleptic treatment produces a suppression of general activity but leaves the motivational properties of food-paired stimuli intact.

Animals↗
PubMed1990

Pimozide prevents the response-reinstating effects of water reinforcement in rats.

Thirsty animals were trained to traverse a straight runway once each day for a reward consisting of 100 licks from a water-filled drinking tube. Once running speeds had stabilized, single daily extinction trials were initiated during which no water reinforcement was provided in the goal box. Extinction trials continued until running had slowed to levels approximately half of that observed during reinforced trials. A single treatment trial was then conducted in which some animals found water in the goal box and others continued to find an empty water bottle. Those subjects that were reinforced on treatment day subsequently demonstrated a reinstatement of their operant running response on the very next trial (i.e., 24 hr later). However, pretreatment with 1.0 mg/kg (but not 0.5 mg/kg) of the dopamine antagonist drug, pimozide, attenuated this response-reinstating effect of water-reinforcement. This action of pimozide was not likely a consequence of some residual sedative or motor incapacitation since a) the test day was conducted 24 hr after the treatment day by which time the pharmacological actions of the drug had greatly subsided; b) a Motor Control group administered pimozide after the reinforced trial exhibited normal response-reinstatement 24 hr later on Test Day; and c) on treatment day, pimozide did not reliably attenuate running times, latency to initiate drinking, nor the rate of licking behavior. Together, these data suggest that dopamine receptor antagonism can produce an attenuation in the reinforcing efficacy of water.

Animals↗
PubMed1990

Haloperidol prevents the reinstatement of amphetamine-rewarded runway responding in rats.

Animals were trained to traverse a straight-alley once each day for a reward of 1.0 mg/kg SC d-amphetamine sulfate. After 14 days of acquisition, extinction trials were initiated in which the amphetamine reward was replaced by injections of physiological saline. After running speeds had decreased to less than one third those of preextinction values, rats received a single amphetamine-rewarded trial either in the absence or presence of haloperidol (0.075, 0.15 or 0.3 mg/kg IP). Twenty-four hours later, animals were tested for reinstatement of operant running in a single drug-free Test trial. Animals that were nondrugged during the amphetamine-rewarded trial demonstrated a statistically reliable increase in running speed on the Test trial relative to extinction baseline speeds. In contrast, animals that were under the influence of medium or high doses of haloperidol during the amphetamine-rewarded trial failed to show Test day increases in running speed. This result did not stem from some residual sedative or performance impairing quality of the drug since a "motor control group" administered a high dose of haloperidol shortly after a rewarded trial, was able to demonstrate unimpaired reinstatement of operant running on Test day (i.e., 24 hr later). These findings support the view that dopamine systems play a role in the neural substrates underlying the incentive motivational properties of amphetamine reinforcement.

Animals↗
PubMed1989

CCK-8 injected into the nucleus accumbens attenuates the supersensitive locomotor response to apomorphine in 6-OHDA and chronic-neuroleptic treated rats.

Postsynaptic dopamine-cholecystokinin (CCK) interactions in the nucleus accumbens were studied in two behavioral preparations of DA receptor supersensitivity: chronic-neuroleptic treated and 6-hydroxydopamine (6-OHDA) denervated rats. Subcutaneous (SC) injections of apomorphine (APO; 0.15 mg/kg) in experiment 1 produced marked hyperlocomotion in rats following 12 days of pretreatment with cis-[Z]-flupenthixol (2 mg/kg; twice per day). Bilateral intra-accumbens (N.Acc.) microinjections of CCK-8 (2 ng and 2 micrograms) reliably reduced APO-stimulated hyperlocomotion. An intermediate CCK dose (20 ng) was without effect. No change in APO responsivity following chronic vehicle treatment was observed and the baseline APO response was not altered by CCK at any dose. Denervation of mesolimbic dopamine (DA) terminals by intra-N.Acc. injections of 6-hydroxydopamine (6-OHDA; 8 micrograms/side) in experiment 2 similarly resulted in intense locomotor hyperactivity after APO stimulation (0.1 mg/kg; SC). Bilateral intra-N.Acc. injections of CCK-8 (1, 10, 100 ng, and 1 micrograms) significantly attenuated the supersensitive locomotor response to APO. As in experiment 1, CCK produced "biphasic" dose-response effects with strong attenuation that persisted throughout the entire 60-min test at both high (1 microgram) and low (1 ng) doses. Intermediate CCK doses (10 and 100 ng) produced only short-term reductions in activity. Hypomotility induced by APO in SHAM-lesioned rats was not effectively reversed by CCK treatments. CCK had no effect on unstimulated baseline locomotor activity in either 6-OHDA or SHAM-lesioned rats. These results provide further evidence that CCK-8 modulates mesolimbic DA activity by functionally opposing the postsynaptic effects of DA in the region of the nucleus accumbens.

Animals↗
PubMed1988

Haloperidol blocks the response-reinstating effects of food reward: a methodology for separating neuroleptic effects on reinforcement and motor processes.

To test the hypothesis that dopamine antagonist drugs attenuate the reinforcing properties of food, rats previously trained to traverse a straight runway for food reward subsequently underwent extinction sessions. After running speeds had substantially decreased, rats received a single food-rewarded trial either in the presence or absence of haloperidol (0, 0.15 or 0.30 mg/kg IP). Twenty-four hours later, animals were tested for reinstatement of the running response during a drug-free test trial. Animals that were nondrugged during the food-rewarded trial showed increases in running speed on the test trial relative to extinction baseline speeds. In contrast, animals under the influence of haloperidol during the food-rewarded trial failed to show test day increases in running speed. Additional control groups ruled out the possibility that the haloperidol results were due to either motor or state-dependent learning effects. The findings support the view that dopamine systems play a role in the neural substrates underlying food reinforcement. In addition, the study demonstrates a simple and effective methodology for separating neuroleptic effects on motor and reinforcement processes.

Animals↗
PubMed1988

Opposite actions of CCK-8 on amphetamine-induced hyperlocomotion and stereotypy following intracerebroventricular and intra-accumbens injections in rats.

Cholecystokinin-octapeptide (CCK-8) has recently been found to coexist with dopamine (DA) in a subpopulation of midbrain DA neurons. The present study investigated the functional nature of this coexistence by testing the effects of intracerebroventricular (ICV) and intra-nucleus accumbens (NAS) applications of CCK-8 in two behavioral assays of DA function (i.e., stimulant-induced hyperlocomotion and stereotypy). Rats were injected with 1 or 3 mg/kg of d-amphetamine sulfate (AMP) 15 minutes prior to ICV (2 micrograms) or intra-NAS (20 ng, 200 ng, or 2 micrograms) injections of CCK-8 or haloperidol (HAL; 5 micrograms). ICV administered CCK-8 was found to antagonize the locomotor stimulatory effects of the low AMP dose, while the same peptide treatment markedly potentiated the stereotypy produced by the high dose of AMP. Similar results were obtained when CCK-8 was microinjected directly into the NAS, with the strongest effects observed following the smallest (i.e., 20 micrograms) dose. These results suggest that both locomotor-antagonizing and stereotypy-potentiating effects of central CCK application depend on CCK-DA interactions in the nucleus accumbens.

Amphetamine↗
PubMed1988

Haloperidol blocks the conditioned place preferences induced by rewarding brain stimulation.

The conditioned place preference test was employed to investigate the effects of neuroleptic challenge on the rewarding properties of lateral hypothalamic stimulation. Conditioning took place during a single day and consisted of five 5-min exposures to each of two environments (differing in color and floor texture). Twenty-four hours later, when provided a choice between the two environments, rats showed strong preferences for the environment in which they had experienced sessions of rewarding brain stimulation. These stimulation-produced place preferences were prevented by pretreatment with the neuroleptic drug, haloperidol (0.3 but not 0.15 mg/kg, ip). On the basis of these results, it was concluded that (a) the conditioned place preference test can provide a rate-free index of brain stimulation reward and (b) dopamine receptor antagonism can result in an attenuation of the rewarding properties of lateral hypothalamic stimulation.

Animals↗
PubMed1986

A partial reinforcement extinction effect in water-reinforced rats intermittently treated with haloperidol.

Thirsty rats were trained to traverse a straight runway for 30 sec access to water reinforcement. The experiment consisted of daily single trials during a 30-day reinforcement phase followed by 21 days of extinction. Animals that experienced no water reward on 33% of the reinforcement trials subsequently demonstrated an increased resistance to extinction of the runway response compared to continuously reinforced (CRF) animals. This "partial reinforcement extinction effect" (PREE) was also observed in CRF animals pretreated with the neuroleptic drug haloperidol (0.075 or 0.15 mg/kg) on 33% of the reinforcement trials. Thus, periodic dopamine receptor antagonism produced behavioral results comparable to those produced by periodic reward omission. These data cannot easily be accounted for by some form of general drug-induced performance deficit since the extinction trials were conducted in undrugged animals. It was concluded that dopaminergic substrates may play a role in mediating the behavioral effects of water reinforcement.

Animals↗
PubMed1986

Effects of haloperidol on the biophysical characteristics of operant responding: implications for motor and reinforcement processes.

Food-deprived rats were reinforced with sweetened condensed milk for pressing a force-sensing operandum on a continuous reinforcement basis. Force was continuously recorded (every 0.00195 sec) during each response, and measures derived from the resulting force-time waveforms served as the basis for evaluating neuroleptic challenge in the form of haloperidol (0.04, 0.08, 0.16 mg/kg). Significant dose-related drug effects included a decrease in response rate, an increase in mean emitted peak force, and an increase in overall response duration. Additional quantitative analyses revealed that the drug-induced increase in response duration resulted primarily from a slowing in the animal's paw removal from the force-sensing operandum. The findings are analogous to deficits in Parkinson's disease and suggest a behavioral mechanism that might account for much of the rate attenuating effects of neuroleptics. Implications for motor and reward interpretations of the actions of dopamine antagonists are also discussed.

Animals↗
PubMed1986

Haloperidol induces a partial reinforcement extinction effect in rats: implications for a dopamine involvement in food reward.

The hypothesis that dopamine antagonist drugs attenuate the reinforcing properties of food was investigated in hungry rats trained to traverse a straight runway for food reward. Testing consisted of a single trial per day during which latencies to leave the start box and to traverse the alley were recorded. In each experiment, a reinforcement phase lasting 30 consecutive days was immediately followed by a 21 day extinction phase. The runway responses of animals that experienced intermittent food reward during the reinforcement phase of the experiments, was later found to be more resistant to extinction than those of continuously reinforced animals. This "partial reinforcement extinction effect" (PREE) was also observed in animals that experienced periodic reductions in the quantity, but not quality, of food reward. Intermittent pretreatment with 0.15 mg/kg of haloperidol during the reinforcement phase produced a PREE that was indistinguishable from that produced by reward omission on those same trials. Control groups for motor debilitation and for non-associative drug effects did not demonstrate a PREE. These results are consistent with the view that central dopamine substrates play a role in the neural basis of food reward.

Animals↗