The effects of intra-subicular ibotenate on resistance to extinction after continuous or partial reinforcement.

Intracerebral injections of ibotenate were used to produce, in rats, extensive cell loss in the subiculum. These rats and sham-operated controls were trained to run in a straight alley for food reward delivered on a continuous (CR) or partial (PR) reinforcement schedule. In controls PR training gave rise to the well-known partial reinforcement extinction effect (PREE), i.e., greater resistance to extinction than that observed in CR-trained animals. Previous experiments have shown that large aspiration lesions of the hippocampal formation eliminate the PREE; and that ibotenate-induced lesions of the subicular region plus either the hippocampus or the entorhinal cortex disrupt it. In contrast to these previous results, the PREE was unaltered in the present experiment by damage largely restricted to the subiculum. This lesion caused only relatively small changes in running speeds during acquisition. Thus the critical region(s) of damage within the hippocampal formation for disruption of the PREE remains uncertain.

The role of dopamine in intracranial self-stimulation of the ventral tegmental area.

The role of dopaminergic (DA) neurons in brain stimulation reward produced by electrical stimulation of the ventral tegmental area (VTA) was investigated in the rat. In the first experiment, extensive 6-hydroxydopamine lesions of the ascending fibers of the mesotelencephalic DA projections resulted in significant changes in intracranial self-stimulation (ICS) rate-current intensity functions when the lesion was ipsilateral to the stimulating electrode. Similar contralateral lesions had no effect on these functions, thus ruling out lesion-induced performance deficits as being responsible for the decreases in ICS rates across the wide range of current intensities that occurred after the ipsilateral lesions. In the second experiment, ICS obtained from electrodes in the VTA resulted in significant increases in the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, nucleus accumbens, and olfactory tubercle ipsilateral to the stimulating electrode. The ratios of DOPAC and HVA to DA, considered to be indices of DA utilization, were also increased in these brain regions ipsilateral to the electrode. No changes were observed in the contralateral striatum, nucleus accumbens, and olfactory tubercle. Similar increases were observed in stimulated "yoked" animals that received brain stimulation at identical rates and currents but did not lever-press for this stimulation. The third experiment examined the effects of lever-pressing for food on an FR8 schedule of reinforcement on DA utilization in the striatum, nucleus accumbens, and olfactory tubercle. Despite high rates of responding, no effects were observed on DOPAC:DA or HVA:DA ratios in these brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between minimum reinforcing doses and injection speed in cocaine and pentobarbital self-administration in crab-eating monkeys.

The relationship between minimum reinforcing doses and injection speed was investigated by using 2 levels of speeds in experiments on self-administration of cocaine or pentobarbital in 2 crab-eating monkeys each. The experiments were conducted under a fixed ratio (FR) 1 schedule with 30-min time-out after each drug injection, wherein the drugs and saline were made available for alternate 5-day periods. The minimum reinforcing doses at each injection speed were determined by the titration procedure in which the presence or absence of reinforcing effect at a particular drug dose was judged based on comparison of the self-administration rate at that dose with the rate in the preceding saline period. The results showed that the minimum reinforcing doses of cocaine and pentobarbital tended to be higher in inverse proportion to the injection speed of the drugs.

Embryonic hippocampal grafts ameliorate the deficit in DRL acquisition produced by hippocampectomy.

Transplants of fetal neural tissue survive and develop in lesion cavities produced in adult rats. The present experiment tested the effect of grafting fetal hippocampal or brainstem tissue on the ability of rats with hippocampal lesions to perform on a differential reinforcement of low response rate (DRL) operant schedule. The DRL interval was 20s. Eighty-six percent of the hippocampal grafts and 69% of the brainstem grafts developed to maturity. Inspection of sections from rats in which the mature transplant had been injected with Fast blue, indicated that these grafts formed connections with the host brain. Consistent with previous reports, rats with hippocampal lesions were impaired in performance of the DRL task. Rats given fetal grafts of hippocampal tissue into the hippocampal lesion site on the day of lesion production were significantly better in performance of the DRL requirement than were lesion-only rats or rats receiving grafts of fetal brainstem tissue. The results of this study confirm that grafts of fetal brain tissue can both develop in a lesion site in an adult brain and ameliorate lesion-induced behavioral deficits.

A neurobiological alternative to the perceptual reinforcement hypothesis of stereotyped behavior: a commentary on "Self-stimulatory behavior and perceptual reinforcement".

A perceptual reinforcement theory of stereotyped movements is advanced by Lovaas, Newsom, and Hickman (1987) in an effort to integrate a number of diverse observations about the origins and maintenance of this behavior. We, in turn, argue that the theory, as presented, is logically flawed and fails to take into account important biological findings and theory concerning pathological stereotyped acts. An alternative theory, derived primarily from neurological concepts, is briefly described.

Increased regularity of activity of cortical neurons in learning due to disinhibitory effect of reinforcement.

This paper reviews the author's studies on neurophysiologic mechanisms of conditioned reflex learning. Electroencephalograms, evoked potentials, activity of neocortical and hippocampal neurons and the rabbits' behavior in the course of elaboration of defensive and inhibitory conditioned reflexes to light flashes have been recorded. Electric shock (ECS) applied to the paw served as reinforcement. The study demonstrated three types of reinforcement effect on the activity of cortical neurons: activating, disinhibitory, and inhibitory. EEG activation due to reinforcement is accompanied by a change in phasic cortical neuronal activity from chaotic or irregular, typical of rest or inhibition, to regular tonic discharges (in neocortex and hippocampus) and group discharges in the stress rhythm, 5-7 Hz in the hippocampus. Following a number of conditioning trials, the effect of reinforcement is simulated by the effect of a conditioned stimulus. With EEG activation and increased regularity in impulses, facilitation of motor reactions is observed.

Neurochemical substrates for opiate reinforcement.

The studies reported herein summarize our work to date aimed at determining the neurochemical substrates for the reinforcing properties of opiates. Rats were trained to self-administer heroin intravenously in daily 3-hour sessions, and pharmacological blockade and neurotoxin-induced lesions were used to define the neurochemical substrates for this reinforcing action. Low-dose DA receptor blockade failed to alter heroin self-administration but significantly increased cocaine self-administration, presumably reflecting a decrease in the reinforcing effectiveness of cocaine. Destruction of presynaptic DA terminals within the N.Acc. produced extinction of cocaine, but not heroin, self-administration. Opiate receptor blockade with systemic naloxone increased heroin, but not cocaine, self-administration. Methylnaloxonium injections into the N.Acc. were effective in increasing heroin self-administration at doses one-eighth those observed for intracerebroventricular injections. Reinforcement has been explored using a place-preference procedure and a self-administration drug-substitution paradigm. Mu/delta agonists such as B-END readily produce a naloxone-reversible place preference. Fentanyl derivatives also produce place preference and substitute for heroin during self-administration. The kappa agonist U50-488 produces place aversion, not place preference, and does not readily substitute for heroin. Altogether, these results suggest that mu/delta receptor subtypes in the region of the N.Acc. may be an important neurochemical substrate for opiate reinforcement.

Brain stimulation and reward: "pleasure centers" after twenty-five years.

"Self-stimulation" is a phenomenon whereby an animal (including a human being) will repeatedly stimulate its brain electrically, sometimes to the point of exhaustion. This phenomenon is robust and readily reproducible in many areas of the brain, particularly in nuclei and fiber tracts known to be monoaminergic, and it has been the basis for the study of reinforcement and learning mechanisms in the brain. The last 25 years of work on intracranial self-stimulation is reviewed with an emphasis on mechanisms, primarily catecholaminergic. Implications for learning and pain mechanisms are discussed.

Comparison of effects of small lesions in posterodorsal septum on spontaneous and rerun correction (contingently reinforced) alternation in rats.

In the first part of the experiment, characteristics of T-maze alternation behavior were compared by giving one group of 11 rats seven sessions under conditions of "rerun correction" (contingent reinforcement for alternation) and another group of 11 rats the same number of sessions with noncontingent reinforcements, i.e., entering either goal arm of the T-maze was reinforced. Both groups alternated significantly above chance, and the difference in medians between groups was small but significant in later sessions. However, rats given rerun correction training quickly came against the "ceiling" of 100% alternation, and individual differences were small. The scores of rats run under conditions of "spontaneous" alternation were more variable, both within and between rats. In the second part of the experiment, six rats in each group received small electrolytic lesions in the posterodorsal septum. There were five operated-control rats from each group. After 2-wk postoperative recovery all rats were again given seven sessions in the T-maze. Under rerun correction procedure (contingent reinforcement), the controls retained near-perfect alternation scores. Most animals with lesions dropped to chance levels but recovered to control level over the seven sessions. Rats tested under spontaneous alternation conditions behaved quite differently. The control group continued to alternate significantly, but rats with lesions significantly alternated less and did not recover.

[Avoidance mechanisms during self stimulation]. / Issledovanie mekhanizmov izbeganiia pri samostimuliatsii

Increased negative discordance of the dominating mode of the pressing duration histogram (PDH), which correlates with the growth of fixed bursts of stimulation is accompanied by a progressive decrease in the reinforcing properties of self-stimulation (SS), avoidance of the pedal and at the same time by a change of behavioral grooming reactions in the intervals between SS for search and consummatory reactions. Hunger considerably shortens the preferable duration of pressing or leads to the appearance of an additional mode on the PDH. With the change of the dominating PDH mode from positive discordance to a negative one, brain stimulation acquires aversive properties which are apparently due to the activation of the mechanisms of specific motivations.