Conditioned taste preference and response rate as measures of brain-stimulation reward: a comparison.
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Animals↗
Biomedical subjects
A Ettenberg
Publications and source records attributed to A Ettenberg.
Conditioned taste preferences as a measure of brain-stimulation reward in rats.
Conditioned taste preferences (CTPs) were demonstrated in rats after one, three or five pairings of a novel tasting solution with sessions of intracranial self-stimulation (ICSS). Control groups that experienced single or repeated unpaired presentations of the novel taste or the ICSS did not exhibit such preferences. Although there were no group differences in the absolute size of the CPTs, the resistance of those preferences to extinction reliably increased with the number of novel taste/ICSS pairings. A second experiment was devised to study the effects of changes in ICSS Current intensity on the CTPs produced by that ICSS. There were statistically reliable differences in the CTPs produced by Low-Current and High-Current groups. A No-Current control group did not demonstrate a CTP. Taken together these data suggest that the conditioned taste preference is a learned phenomenon analogous to the conditioned taste aversion that occurs following novel taste/illness pairings. The use of the CTP paradigm as a measure of the rewarding nature of intracranial self-stimulation is proposed.
Animals↗
Performance effects with repeated-response measures during pimozide-produced dopamine receptor blockade.
Rats were trained to lever-press for either food reward or brain-stimulation reward on a continuous reinforcement schedule. Following training each animal was extinguished (i.e. tested with the reward omitted) under the influence of pimozide (0.25 mg/Kg or 0.5 mg/Kg). Pimozide produced a dose-dependent reduction in the mean number of responses to extinction made by rats in ecach group. In a second experiment, pimozide produced a similar dose-dependent decrease in the performance of a naturally occurring behavior (nose-poking) that had never been associated with reward. These data suggest that dopamine receptor blockade can produce a perofrmance deficit in situations which require repetitive responses, and that this deficit is unrelated to the presence or absence of reward.
Animals↗
Conditioned taste preferences in the rat induced by self-stimulation.
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Animals↗
Effects of dopamine supersensitivity on lateral hypothalamic self-stimulation in rats.
Dopamine (DA) receptor supersensitivity was demonstrated by potentiated d-amphetamine stereotype after a three-day treatment regimen in which the DA receptor blocker pimozide (4.0 mg/kg) was administered twice daily. Similarly-induced DA supersensitivity produced a significant increase in the rate of lever-pressing for lateral hypothalamic (LH) intracranial self-stimulation (ICSS) and a significant decrease in ICSS thresholds. No change from pretreatment baselines was observed in vehicle-treated control animals. Following three-day treatment with the noradrenaline--(NA) and DA-receptor blocker, haloperidol (4.0 mg/kg twice daily), a single injection of the alpha-adrenergic agonist clonidine (0.15 mg/kg) caused increased running behavior. In contrast clonidine decreased running in rats pretreated with chronic pimozide or vehicle. These results indicate an increase in the sensitivity of central NA receptors following chronic haloperidol but not chronic pimozide. Taken together, these findings were interpreted as a potentiation in the reinforcing properties of LH-ICSS after chronic pimozide treatments due to increases in the sensitivity of DA and not NA receptors.
Animals↗
Non-selective enhancement of locus coeruleus and substantia nigra self-stimulation after termination of chronic dopaminergic receptor blockade with pimozide in rats.
Self-stimulation of substantia nigra and locus coeruleus were assessed before and after an 8-day regimen in which pimozide was given twice daily at a dose of 0.5 mg/kg (first 4 days) or 1.0 mg/kg (last 4 days). At 48 hours after termination of pimozide treatment self-stimulation was increased to 25% above pre-pimozide baseline levels: this was true for both self-stimulation sites. Rates remained high the following day but returned to normal by the third day of post-pimozide-testing. These data are interpreted as reflecting pimozide-induced supersensitivity in a dopamenergic substrate. This substrate appears to be critical for intracranial self-stimulation even when its fibers are not themselves activated at the tip of the stimulating electrode.
Animals↗
Effects of chronic lithium on enkephalin systems and pain responsiveness.
We have recently undertaken an extensive examination of the effects of chronic dietary lithium treatment on levels of brain leucine-enkephalin immunoreactivity (1-enk-IR), release of endogenous 1-enk-IR from globus pallidus prisms in vitro and behavioral responsiveness to pain. Two LiCl containing diets were used. Rats on the lower strength diet attained brain Li levels of 0.40-0.55 mEq/L, while those on the higher strength diet attained levels of 0.70-1.0 mEq/L. In one series of experiments, we sought to relate alterations of K+-stimulated, Ca++-dependent release of 1-enk-IR to alterations of the content of the peptide. After 1 week on the lower strength diet, neither measure was affected in any of the brain regions examined. Following 2 or 3 weeks of feeding with the lower strength diet, 1-enk-IR levels in the globus pallidus and nucleus accumbens were elevated. However, 3 weeks of the high strength Li diet did not lead to alterations of 1-enk-IR content. In contrast, the release of 1-enk-IR was potentiated but only in subjects in which the brain lithium exceeded a threshold level. In another series of studies, we observed that hot-plate escape latency was significantly elevated in rats fed the high strength Li diet for 3 weeks. Also, the Li-treated animals had a greater morphine-induced elevation of escape latency than controls; this effect was less effectively blocked by naltrexone. These findings suggest that chronic exposure to Li leads to transiently elevated levels of 1-enk, and, when brain Li levels are greater than 0.5 mEq/L, to a potentiation of endogenous enkephalin release. The analgesia in Li-treated subjects may eventually be related to these influences of the anti-manic drug on enkephalinergic neurotransmission.
Analgesia↗
Concurrent positive and negative goalbox events produce runway behaviors comparable to those of cocaine-reinforced rats.
Rats traversing a straight-alley for reinforcing stimuli typically exhibit faster running times as training proceeds. In previous work from this laboratory, animals running for a reinforcement consisting of intravenous infusions of cocaine, unexpectedly demonstrated a progressive increased time to enter the goalbox over trials. Closer observation revealed that the animals were exhibiting a unique retreat behavior (i.e., stopping their forward advance toward the goalbox and returning toward the startbox). It was hypothesized that the retreat behavior reflected an inherent conflict that originated from concurrent positive and negative associations with the goalbox. Such associations were attributed to cocaine's dual and well documented reinforcing and anxiogenic effects. To test this idea, the present study compared the runway behavior of animals that concurrently received food and mild foot shock in the goalbox to the behavior of the other animals running for cocaine. Results demonstrated that food + shock reinforced animals took longer to enter the goalbox and made more retreats than a control group that received only food in the goalbox. Both these effects were reversed by pretreatment with the anticonflict, anxiolytic drug, diazepam. The behavior pattern of animals that received the combination of food and footshock was found to strongly resemble that of IV cocaine-reinforced rats, a result consistent with the notion that chronic cocaine administration has both positive and negative consequences.
Analysis of Variance↗
Dopamine, neuroleptics and reinforced behavior.
Animals working for any one of a variety of positive reinforcers (food, water, brain-stimulation...) produce dramatic decrements in operant performance when challenged with dopamine antagonist neuroleptic drugs. This well-established fact has generated considerable research aimed at identifying the precise nature of the drug-induced behavioral impairment. The two most oft-cited hypotheses suggest that much of the reduction in operant responding can be accounted for by either an "anhedonic" or "motoric" consequence of dopamine antagonism. Several novel behavioral paradigms are described which were devised to more clearly elucidate both the motor and reward impairing qualities of neuroleptic agents. Motor performance was assessed in a food-reinforced task in which a computer-operated force-transducer was used to obtain detailed analyses of the biophysical properties of operant responding. These studies suggested that neuroleptics impair the temporal nature (i.e., "timing") of normal operant behavior and not the physical capacity of the animals (i.e., the ability to emit "force"). This identification of a robust "slowing" effect of neuroleptic challenge, suggested that the investigation of putative "reward" impairments should best be conducted with behavioral paradigms in which the test data are collected from undrugged animals. Three such paradigms are described: a partial reinforcement extinction test, an incentive motivation test, and a conditioned place preference test. To date, our results suggest that when motor confounds are avoided, dopamine antagonist drugs can still produce patterns of operant behavior that very closely resemble those observed with actual reductions in reward magnitude. Such data provide support for the contention that central dopaminergic substrates play a role in the neurobiology of positive reinforcement.
Animals↗