Bar Press Research Articles

Effects of acute and chronic fenfluramine on self-stimulation and its facilitation by amphetamine

DL-Fenfluramine (20 mg/kg) releasing serotonin and amphetamine (2 mg/kg) releasing dopamine were given to adult rats trained to bar press for electrical stimulation to the medial forebrain bundle. Amphetamine treatment enhanced lever-pressing for 1–2 h. A single fenfluramine treatment rapidly suppressed self-stimulation with slow recovery in 5–7 days to a rate below the initial basal rate. A second treatment a week later again suppressed response rate and rates returned to a still lower baseline. Combined fenfluramine-amphetamine treatment at this time transiently abolished lever pressing for 1–3 h followed by 9–11 h of enhanced responding. The serotonin antagonist, ketanserine (0.1 mg/kg), but not cyproheptadine (0.1 mg/kg i.p.), partially protected against the effects of fenfluramine. The serotonin agonist, quipazine (0.5 mg/kg), but not dimethoxyiodophenylisopropylamine (DOI) (2.2 mg/kg), partially substituted for fenfluramine in the combined treatment. Fenfluramine markedly depleted serotonin and 5-hydroxyindoleacetic acid in frontal cortex, hippocampus, and caudate putamen. Ventral and midline midbrain regions were less affected. Combined fenfluramine and amphetamine treatment elevated dopamine levels in frontal cortex, hippocampus and caudate-putamen, but not in midbrain. These findings support a serotonin-dopamine interaction in self-stimulation behavior and suggest that repeated fenfluramine treatment results in chronic low level serotonergic stimulation and diminished serotonin storage capacity.

Capsaicin does not attenuate bombesin-induced suppression of operant responding for food reward

Systemic treatment with capsaicin, a neurotoxin which damages unmyelinated peptide-containing sensory neurons, has been shown to attenuate bombesin (BBS)-induced suppression of food intake. To determine whether capsaicin-sensitive fibers mediate the effect of BBS on appetitive motivation, we examined BBS-induced suppression of operant responding in rats pretreated neonatally with capsaicin (50 mg/kg; SC) or control vehicle. At 8–10 weeks of age, rats were trained to bar press for food. After achieving a stable level of performance, the animals were injected with BBS (10 μg/kg), normal saline, or prefed with 20 Noyes 45-mg pellets. Animals were then tested in an operant chamber on an FR 5 schedule of reinforcement for one hour. The results indicated that BBS suppressed bar pressing, regardless of whether animals were pretreated with capsaicin or control vehicle. These findings are inconsistent with the hypothesis that BBS induces satiety via capsaicin-sensitive neurons. The results suggest the possibility that more than one mechanism may mediate the effects of BBS: a neural mechanism involved in consummatory responses and a humoral mechanism involved in the operant response.

Responses of lateral hypothalamic glucose-sensitive and glucose-insensitive neurons to chemical stimuli in behaving rhesus monkeys.

1. Extracellular single neuron activity was recorded in the lateral hypothalamic area (LHA) of awake, behaving monkeys, with particular regard to the feeding-related functional characteristics of glucose-sensitive (GS) versus glucose-insensitive (GIS) neurons. Firing rate changes were recorded by means of carbon fiber, multibarreled glass microelectrodes during 1) microelectrophoretic application of various chemicals, 2) gustatory and olfactory stimulation, and 3) a high fixed-ratio schedule (FR) bar press feeding task. 2. In 336 neurons examined, 91 (27%) were suppressed by electrophoretically administered glucose, and so they were designated as GS cells. The 245 neurons (73%) in which the firing rates did not change during glucose applications were pronounced GIS. The 179 GS and GIS cells tested exhibited different responses to the catecholamines (CAs), noradrenaline (NA) and dopamine (DA), both of which are intimately involved in the control of feeding. More GS neurons responded to NA than did GIS cells; the predominant effect of both CAs on GS neurons was inhibition. 3. The taste responsiveness of 111 LHA neurons was examined. Fifty-seven cells (52%) showed responses to gustatory stimulation. Of 50 GS neurons tested, 33 (66%) exhibited firing rate changes to tastes. On the contrary, only 24 (39%) of the 61 GIS neurons examined responded to gustatory stimuli. Activity changes of GS neurons commonly occurred to two or more tastants, in distinction to the relative gustatory specificity shown by GIS cells. 4. Two hundred fifty-six (84%) of the 303 neurons tested responded during one or more phases of the bar press feeding task. Most activity changes occurred during the bar press (BP) and reward (RW) periods, however numerous phasic responses to cue light (CL) and cue tone (CT) were also observed. A higher proportion of the GS neurons showed task-related activity changes than did the GIS cells (77, 95% and 179, 81%, respectively). GS neurons responded more during the BP phase and to the food reward; GIS cells were more responsive during the CL that enabled acquisition and the CT that signaled reward. Thus GS neurons were responsive during the acquisition and consumption of reward, whereas GIS cells responded to external cues signaling both of these events. The gustatory neurons displayed specific task-related activity changes only in the CL (GIS cells) and BP phases (GS neurons), that is, in phases most intimately involved in sensory-motor integration. 5. Two-thirds of the 30 GS neurons tested were responsive to both gustatory and olfactory stimulation as opposed to only one-third of GIS cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracranial self-stimulation motivates weight-lifting exercise in rats

The purpose of this study was to determine the feasibility of using a positive reinforcement protocol to motivate weight-lifting exercise in rats. Intracranial self-stimulation was used to induce weight-lifting exercise. Bipolar electrodes were implanted in the ventral tegmental area of rats, and the animals were trained to bar press on a continuous reinforcement schedule for electrical brain stimulation. Animals with response rates of 1,200-1,500 presses/h were then trained with a discriminative light stimulus to alternate between a normally positioned bar and an elevated bar that could be reached only by standing on the hindlimbs. The animals were fitted with a weighted jacket at a starting resistance of 5-10% of their body weight. Weight-training sessions were conducted 5 days/wk for 10 wk. Training consisted of 600 presses/session, alternating every 15 presses between the low and high bars. At the beginning of each subsequent week, the resistance was progressively increased, with some animals eventually training at resistances greater than 50% of their body weight. At the end of the training period, the rats were lifting over 550% of the starting weight. Gastrocnemius size and mean fiber diameter were increased in the weight-lifting animals. This model combines exercise with positive incentive and has the advantages of being relatively easy to implement and not producing any apparent physical or mental trauma in the animal.

Taste and olfactory modulation of feeding related neurons in behaving monkey

Single neuron activity in the monkey lateral hypothalamus (LHA) was recorded by multibarreled electrode during a bar press feeding task. Activity of glucose-sensitive (GS) neurons decreased during bar press (BP) and reward (RW) periods. The inhibition was caused by activation of β-adrenoceptors and opioid receptors respectively. Glucose-insensitive (GIS) neurons were excited during BP and RW, and at cue light (CL). Excitation at CL and BP was caused by activation of dopaminergic receptors. Among GS neurons, 66% responded to taste and 88% to odor. These responses were 39% and 52% in GIS neurons. GS neurons responded predominantly to two or more taste and odor stimuli while GIS neurons responded to only one stimulant. GS neurons have dense mutual connections with the prefrontal area, and GIS neurons are connected with the motor area. Gustatory and olfactory stimulation elicited responses in 67% of GS neurons and in only 21% of GIS neurons. Data suggest that GS and GIS neurons may have different functions in feeding: GS neurons process endogenous chemical information and integrated chemical sensations, and GIS neurons process external information processing, motor control and discriminative chemical sensations.

Stimulation in prefrontal cortex inhibits conditioned increase in blood pressure and avoidance bar pressing in rats

In our previous work, it was established that stimulation in a precisely defined area of the prefrontal cortex and in nucleus accumbens inhibits motor and cardiovascular components of the defence reaction elicited by stimulation in hypothalamus or amygdala, but it did not inhibit operant appetitive bar pressing. In the present investigations it was shown that electrical stimulation in the same area of prefrontal cortex and in the nucleus accumbens inhibited blood pressure increases elicited by a conditioned sound. In another set of experiments it was also shown that it inhibited bar pressing developed with Sidman's schedule. It is therefore concluded that inhibition originating in the described region of the prefrontal cortex is specifically addressed to motor and cardiovascular components motivated by fear or aggression.

EFFECTS OF REINFORCING PRESELECTED APPROXIMATIONS ON THE TOPOGRAPHY OF THE RAT'S BAR PRESS

The effects of different shaping approximations on the topography of the rat's bar press were investigated in two experiments. Behavior was classified into discrete components, and changes in components and their sequential organization were analyzed. Experiment 1 examined response form early in training and found that specific components reinforced during shaping were incorporated into press sequences. Experiment 2 investigated how response form changed when a shaping contingency was relaxed later in training. Two topographies were selected for reinforcement, and both appeared in the press sequences of all subjects by the end of shaping. Subsequently, all variations of bar pressing were reinforced, and neither topography was necessary to satisfy the contingency. Although the frequency of the topographies reinforced during shaping declined for 3 of 4 subjects during this phase, the most frequent press sequence for 2 rats at the end of training included both unnecessary topographies. Variability in press topographies declined when all emitted variants were reinforced. However, all subjects emitted novel response forms throughout training. The results demonstrate that specific response-reinforcer contingencies influence response form by modulating component availability and organization.

THE RELATIONSHIP BETWEEN FEEDING RATE AND PATCH CHOICE

Rats in a laboratory foraging simulation searched for sequential opportunities to feed in two patches that differed in the rate at which food pellets were delivered (controlled by fixed-interval schedules) and in the size of the pellets. The profitability of feeding in each patch was calculated in terms of time (grams per minute) and in terms of effort (grams per bar press). These values were the result of the imposed fixed interval, the size of the pellets, and the rate at which the rats pressed the bar in each condition. The rats ate more food and larger meals, but not more frequent meals, at the patch offering the higher rate of food consumption, calculated as grams per minute. The relative intake at any patch was a function of the relative rate of intake during meals at that patch compared to the other patch. Rats respond to explicit manipulations of feeding time in the same manner as they respond to manipulations of feeding effort.

Limbic networks and associative learning: I. Entorhinal contributions to instrumental conditioning

The hippocampal formation is a highly delineated brain structure that is believed to play a prominent role in learning and memory. The present experiment evaluated the contributions of medial and lateral perforant path input to bar press-conditioning under (a) continuous and (b) differential reinforcement of low rates of responding (DRL) schedules, and (c) shuttlebox avoidance conditioning. Bilateral deafferentation of either pathway had no effect on the acquisition of bar press responses or on performance under the DRL schedule. Deafferentation of the medial pathway facilitated acquisition of avoidance responses in a manner much like the effects seen in hippocampectomized animals. It is suggested that the medial perforant path participates in the expression of correlated patterns of neuronal discharge known to develop within the hippocampus and that this “model” serves to modulate the temporal characteristics of simple conditioned reflexes. Loss of the modulatory influence of the model may affect acquisition and extinction rates. Contributions of other hippocampal circuits are discussed in relation to established deficits.

Complex attributes of lateral hypothalamic neurons in the regulation of feeding of alert rhesus monkeys

To elucidate the roles of glucose-sensitive (GS) and glucose-insensitive (GIS) cells of the lateral hypothalamic area (LHA), single neuron activity was recorded during 1) microelectrophoretic administration of chemicals, 2) a conditioned bar press feeding task, 3) gustatory, 4) olfactory, and 5) electrical brain stimulation. GS and GIS neurons showed different firing rate changes during phases of the task, and the responses were highly influenced by the palatability of the food and the motivational (hunger or satiety) state of the animal. The two groups of cells also differed in their responsiveness to gustatory and olfactory stimuli: GS neurons were more likely to respond to tastes and odors than GIS cells. Taste- and odor-responsive GS neurons were primarily suppressed by electrophoretically applied noradrenaline and were localized ventromedially within the LHA. The chemosensitive GIS cells, being organized along a dorsolateral axis, were especially excited by dopamine. The two sets of neurons had distinct connections with associative (orbitofrontal, prefrontal) cortical areas. GS and GIS cells, thus, appear to have differential and complex attributes in the control of feeding.

Application of in vivo electrochemistry to the measurement of changes in dopamine release during intracranial self-stimulation

Stearate-modified graphite paste recording electrodes were acutely or chronically implanted into the nucleus accumbens along with bipolar stimulating electrodes in the ipsilateral ventral tegmental area (VTA). Chronoamperometry was used to monitor changes in electrochemical signals that may correspond to the oxidation of dopamine (DA) during experimenter-administered stimulation (EAS) and intracranial self-stimulation (ICS). Application of EAS to stimulating electrodes in the VTA produced increases in the electrochemical signal in both the anesthetized and conscious preparation. The magnitude of both effects increased as a function of current intensity. Initiation of ICS was also accompanied by an immediate increase in the electrochemical signal. Rate-intensity experiments revealed a corresponding increase in both the ICS rates and the electrochemical signal with successive increases or decreases in current intensity. In subsequent experiments, intraperitoneal injections of DA uptake blockers nomifensine and GBR-12909 produced significant increases in the amplitude of the chronoamperometric signal which corresponded to drug-induced increases in bar press rates. The noradrenergic uptake blocker desipramine had no significant effect on either ICS rates or oxidation current. These data indicate that ICS of the VTA may produce concurrent increases in DA neurotransmission in the nucleus accumbens. The pharmacological studies are consistent with a dopaminergic substrate of brain stimulation reward at electrode sites in the VTA.

Lever-press conditioning in the crab

An operant chamber has been developed for studying lever-press conditioning in the green crab Carcinus maenas. In one series of experiments, animals were presented with a single bar and were reinforced with food for every bar press. Performance increased over time and high rates of responding were observed after 2 days of training. The response rate was always higher than that for a yoked (noncontingent) control group. When the contingencies were switched, the animals adjusted to the new conditions. Discrimination in the lever-press apparatus was demonstrated in a second experiment in which crabs had to choose between two bars, one (S+) caused food to be dispensed while the other (S−) was inactive. Experimental animals pressed the S+ bar at a significantly higher rate than the S− bar. When the contingencies associated with the lever were reversed, animals learned to switch to the correct bar by the second day. It was not necessary to reinforce every response: animals maintained high rates of responding on a schedule where every other response was reinforced. Animals used different methods of pressing the bar; the most common was extension of the claw, predominantly at the meropodite-carpopodite joint.

Discontinuation of diazepam and sensitivity to a shock signal: Fear conditioning prior to drug treatment

The present experiment examined the disruptive capacity of a shock CS when Pavlovian training was completed prior to repeated daily treatment with diazepam (DZ). Two groups of rats were given 20 Pavlovian fear conditioning trials (two per day) to establish a light CS as a shock signal. Both groups were then trained for 15 daily sessions to bar press for food reinforcement. Before each session, one group was injected IP with 5 mg/kg DZ and the other with saline. All injections were discontinued after the last training session. Nine days later, the capacity of the CS to disrupt bar pressing was tested. The CS produced greater disruption of bar pressing for rats that had previously received chronic diazepam treatment. The results suggest that DZ discontinuation increases sensitivity to cues established as fear elicitors prior to initial administration of DZ.

Frequency-response characteristics provide a functional separation between stimulation-bound feeding and self-stimulation

Many lateral hypothalamic electrodes that support self-stimulation also elicit feeding. Refractory period and conduction velocity estimates for the axons supporting these behaviors appear identical, suggesting that these behaviors may be elicited by stimulation of a common directly activated substrate. However, it is not known if the substrate(s) for the two behaviors integrate activity in directly stimulated axons similarly in controlling their respective behaviors. This study generates rate-frequency curves for a range of current intensities for self-stimulation and stimulation-bound feeding, using bar press rate and ingestion rate, respectively, as behavioral measures. For self-stimulation, as is well established, increases in intensity shift rate-frequency curves toward lower frequencies. For stimulation-bound feeding, increases in intensity raise asymptotic ingestion rate, but do not always appreciably change the location of the curve along the frequency axis. The different parametric profiles obtained for the two behaviors suggest different processes of integrating neural activity in the directly activated substrates.

The long-term effects of diazepam, lorazepam, and buspirone on behavioral suppression by a shock signal

1. Two experiments examined the long-term effects of treatment with buspirone (a nonbenzodiazepine anxiolytic), diazepam, or lorazepam (two pharmacokinetically distinct benzodiazepines) on the capacity of a shock cue to disrupt appetitively conditioned behavior. 2. In Experiment 1, rats were injected with diazepam (5 mg/kg), buspirone (1.5 mg/kg or .75 mg/kg), or saline shortly before each of 12 bar press training sessions. Injections were suspended and three days later the rats received five days of Pavlovian fear conditioning (bars removed) in which a tone signaled shock. The capacity of the tone to disrupt bar pressing was then assessed. 3. Bar pressing of rats previously injected with diazepam was more suppressed by the shock cue than that of rats previously injected with buspirone or saline. The long-term effects of buspirone and saline did not differ. 4. In Experiment 2, lorazepam had effects different from diazepam during bar press training. Nonetheless, rats previously injected with lorazepam were also more disrupted by a shock cue than were controls. 5. The results suggest that one long-term consequence of treatment with benzodiazepines may be hypersensitivity to behavioral disruption by stimuli that presumably elicit fear or anxiety.

"Temporal summation decay" in hypothalamic self-stimulation: Threshold changes at long intrapair intervals due to axonal subnormal periods.

Rats were trained to bar press for trains of conditioning (C) and test (T) pulses delivered via lateral hypothalamic electrodes. As intrapair (C-T) intervals increased from 10 ms to 100 ms, the frequency of pulses required for self-stimulation increased, similar to results of Smith and Coons (1970). This effect was observed only for electrode placements where self-stimulation was obtained at frequencies below 16 Hz and currents of 600 microA and higher. The effect was larger when the train duration was increased from 0.5 s to 2.0 s. The threshold increase was abolished when the T pulses were greater in current than the C pulses but not when C pulses were larger than T pulses. The larger T pulses also removed relative refractory period effects at a C-T interval of 1.0 ms. Therefore, the increase in required current or frequency at long C-T intervals appears to be due to a decline in axonal excitability (i.e., the subnormal period) rather than a decay in synaptic temporal summation. Possible flaws in other reports of paired-pulse "temporal summation decay" at long C-T intervals using 2 electrodes are discussed.

Activity and distribution of learning-related neurons in monkey (Macaca fuscata) prefrontal cortex.

The involvement of monkey (Macaca fuscata) prefrontal cortex (PFC) neurons in motor output decisions was studied by recording single neuron activity during 3 tasks: (a) go-left, go-right, or no-go decisions, (b) operant bar press feeding based on discrimination of food and nonfood, and (c) either delayed matching-to-sample (DMS) or DMS with response delay. Combinations of single neuron responses during the 3 tasks suggested 7 types of PFC neurons that were related to attention, choice, task-unique memory, reward anticipation, laterality, initiation of movement, and suppression of movement. The authors suggest that responses of PFC neurons do not depend on physical properties of the stimuli, but on their behavioral significance. PFC neurons might be important for appropriate behavior in response to external stimuli and internal or motivational factors.

Central injections of growth hormone-releasing factor increase operant responding for food reward

1. 1. Male Wlstar rats were prepared with chronic ventricular cannulae and trained to bar press for food pellets in operant cages. 2. 2. Some rats were given icv injections of 0 (vehicle), 0.4, 4.0 and 40.0 picomole GRF on separate days and tested on a continuous reinforcement (CRF) reward schedule. 3. 3. Other rats were given iev injections of 0 (vehicle) and 4 plcomole GRF on separate days and tested on a progressive ratio (PR) reward schedule. 4. 4. In comparison with vehicle injections, GRF significantly increased the average response rate under the CRF schedule and the average breaking point under the PR schedule. 5. 5. The Increased operant responsiveness displayed by rats suggests that central GRF possesses motivational efficacy, increasing the relative reinforcing strength of food.

Stimulation in prefrontal cortex area inhibits cardiovascular and motor components of the defence reaction in rats

In the present investigation it was shown that electrical or chemical ( d,l-homocysteic acid, DLH) stimulation in a defined area of the medial prefrontal cortex inhibits cardiovascular components of the defence reaction elicited by stimulation in the basal nucleus of the amygdala or in the hypothalamus in rats anaesthetized by Saffan. Electrical stimulation in the dorsal part of the nucleus accumbens or ventral part of the nucleus caudate had the same effect, while chemical stimulation (DLH) in these areas was not effective. In unanaesthetized rats stimulation in the prefrontal cortex or the nucleus accumbens inhibited cardiovascular and motor components of the defence reaction induced from the amygdala or hypothalamus. Stimulation in the described areas of the medial prefrontal cortex or nucleus accumbens does not induce general inhibition of motor activity since it did not affect operant, appetitive bar pressing. It is therefore concluded that the inhibition is selectively addressed to the motor activities associated with the defence reaction. It is suggested that inhibition of the cardiovascular components of the defence reaction must occur below hypothalamic level. The inhibition is most likely presynaptic since stimulation in the prefrontal cortex or nucleus accumbens alone did not produce any cardiovascular changes. It is unlikely that the efferent pathway originating in the prefrontal inhibitory area relays in the nucleus accumbens since microinjection of DLH into this nucleus was ineffective. Stimulation in ‘sympatho-inhibitory’ areas (anterior hypothalamus, anterior cingulum) or in the nucleus raphe obscurus had no inhibitory effect on the cardiovascular components of the defence reaction.

Influence of acetylcholine on neuronal activity of monkey amygdala during bar press feeding behavior

Single neuron activity in the monkey amygdala was investigated during cue signalled conditioned bar press feeding behavior and the effects of electrophoretically applied acetylcholine (ACh) and atropine were analyzed. ACh increased the firing rate of one third of the neurons tested; these excitatory responses were inhibited by the muscarinic receptor antagonist atropine. No characteristic location of ACh-sensitive neurons was found, cells were diffusely distributed throughout the amygdala. Activity of ACh-sensitive neurons did not correlate with any particular event during the bar press feeding task. However, continuous application of ACh at low current intensity during the task significantly enhanced the task-related excitatory firing patterns, or markedly attenuated the inhibitory responses. Continuous application of atropine elicited or enhanced inhibitory response patterns. These results suggest that the cholinergic system of the monkey amygdala facilitates neuronal excitation but attenuates inhibition related to various phases of feeding behavior, such as to cue recognition, food aquisition and rewarding process.