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A behavioural and neurochemical analysis of chronic and selective monoamine oxidase inhibition.

The effects of clorgyline were compared with the effects of (-)-deprenyl using measures of rewarding hypothalamic self-stimulation, regional monoamine metabolism and monoamine oxidase activity. Male Wistar rats trained to self-stimulate at half-maximal rates with unilateral bipolar lateral hypothalamic electrodes on a continuous reinforcement schedule were implanted subcutaneously with osmotic minipumps which delivered 1 mg X kg-1 drug per day or vehicle for 13 days. A response rate/stimulation frequency (reward summation) function was determined the day before minipump implantation and on days 5 and 13 of drug administration. Only clorgyline induced a shift to the left in the reward summation function at 5 and 13 days, indicating enhancement of reinforcement. Clonidine (50 micrograms X kg-1 IP) probe tests were run on days 2 and 10 to determine the sensitivity of alpha 2-noradrenaline receptors. Clorgyline induced an attenuation of the clonidine response on day 10 relative to day 2. The other groups exhibited no change in response to clonidine. Clorgyline also induced a progressive increase in self-stimulation rates; this effect was not observed with the other groups. The clorgyline effects were accompanied by an increase in regional brain levels of dopamine, noradrenaline and 5-hydroxytryptamine and a reduction of their acid metabolites. Clorgyline selectively inhibited type A monoamine oxidase, whereas (-)-deprenyl selectively inhibited type B monoamine oxidase.

Animals↗

[Morphine self-administration added to food conditioning: methodological variant in rats].

Rats with permanent intra-jugular cannula are submitted to an alimentary operant reinforcement schedule with fixed ratio type FR 1, FR5, then FR 20. As a result, the animals are self administering (together with the alimentary inducer) a slow (about 5 sec) intravenous infusion of morphine (0.05 mg/kg). 20 per cent only of the experimental population exhibit a psychogenic dependance afterward. On the other hand, the animals for which morphine self-administration has been substituted to the alimentary reinforcement without respecting a transitory period combining both types of reinforcement have never shown any tendancy toward morphine self-administration. The lack of positive results could be related to the marked duration of the self-injection.

Animals↗

Weak inhibitory behavioral effects of postnatal! preweaning taurine injections in rats.

The behavior of rats injected once every 2 days between Postnatal Days 4 and 20 with 62.5 mug/g or 125 mug/g body weight of taurine was compared with saline- or .5 M NaCl-injected litter-mate controls. Taurine-injected rats ran significantly less in the running wheel test and displayed lower response/reinforcement ratios following step-like changes in DRL reinforcement schedules. The quicker adjustments to the changes in DRL schedules did not occur immediately but during sessions following the change. We concluded that taurine administration during early juvenile development could weakly influence adult inhibitory behavior.

Animals↗

Opioid-receptor blockade reduces nose-poke self-stimulation derived from medial entorhinal cortex.

Rats were trained to nose-poke for intracranial self-stimulation (SS) with electrodes unilaterally implanted in the medial entorhinal cortex. The acute effects of naloxone (NX; 0.1-10 mg/kg, IP) on a continuous reinforcement schedule were determined. Reductions in the self-stimulation rates occurred only at moderate doses (median of individual changes = -36% at 1 and 5 mg/kg), whereas the high dose (10 mg/kg) was ineffective. None of the doses influenced operant behavior. These results are consistent with the hypothesis that endogenous opioid-opiate receptor mechanisms play a modulatory role in SS reward. Considering that NX was administered systemically the action of the drug on reinforcement levels may be mediated by a site distinct from the locus of stimulation.

Animals↗

Motivational influences underlying prolactin-induced feeding in doves (Streptopelia risoria).

Prolactin (Prl) increases food consumption in ring doves (Streptopelia risoria) and may promote the hyperphagia exhibited by parent doves when provisioning young. These experiments tested whether Prl also enhances appetitive aspects of feeding behavior. Prl elevated pecking rates in food-restricted doves on a variable-interval (VI) reinforcement schedule and supported continued responding when doves were returned to ad-lib feeding. Prl-treated doves learned the key-pecking response when food intake was clamped at ad-lib levels exhibited before Prl treatment but not when given free access to food. Median break points on a progressive ratio schedule were 2-3 times greater in food-restricted doves than Prl-treated, food-clamped doves even though response rates were similar on VI schedules. These results indicate that Prl enhances appetitive aspects of feeding, although food restriction at the level imposed in this study was more effective in this regard.

Animals↗

Dextromethorphan reduces intravenous cocaine self-administration in the rat.

Dextromethorphan is a widely used antitussive agent with non-competitive antagonistic effects at the excitatory amino acid receptors of the NMDA type. Since excitatory amino acid neurotransmission has been implicated in cocaine dependence, the aim of the present study was to evaluate the effects of acute systemic administration of dextromethorphan in rats trained to self-administer cocaine intravenously. The experiments were designed to evaluate the effects of dextromethorphan on responding for cocaine and cocaine reward magnitude. The hypothesis was that dextromethorphan could attenuate specific aspects of cocaine-seeking behavior thus providing a preclinical rationale for its clinical use. The results reported reveal that acute pretreatment with dextromethorphan (10-50 mg/kg i.p.) significantly reduced cocaine self-administration in rats self-administering the drug intravenously in a simple continuous reinforcement schedule. In addition, acute pretreatment with an effective dose of dextromethorphan (25 mg/kg) decreased cocaine self-administration in rats tested at various doses of cocaine (0.12-0.5 mg/injection). Finally, dextromethorphan (25 mg/kg) also reduced the absolute reward magnitude of cocaine as measured by responding for cocaine in a progressive ratio schedule. These results encourage further experimental and clinical studies to evaluate the potential use of dextromethorphan during various phases of the natural history of cocaine dependence in humans.

Animals↗

Psychological principles of burn wound pain in children. I: theoretical framework.

Burn injuries and the care of burn injuries are punishing experiences for hospitalized children. Pain, novelty, and altered reinforcement schedules elicit instinctive escape and avoidance behaviors that complicate wound care. An understanding of the psychological principles that underlie these complex, complicating behaviors paves the way for effective cognitive and behavioral interventions. In this first article of a two-part series, we use the principles of classical conditioning, operant conditioning, and control coping to describe the developmentally normal emergence of avoidance behaviors that are incompatible with burn wound care. Then, using brief case examples, we outline how classical conditioning transforms neutral stimuli into anxiety-producing, fearful stimuli, how operant behaviors are intentionally or unintentionally reinforced, and how the umbrella of reduced control in the novel hospital environment makes coping difficult for children. We conclude by discussing obstacles to effective application of cognitive and behavioral strategies for the enhancement of control and of compliance with wound care.

Adaptation, Psychological↗

Stimulus control of instrumental reflexes in dogs: a comparison of alimentary and avoidance behaviors after prefrontal damage.

Two experiments involving parallel procedures to investigate stimulus generalization in prefrontal dogs under alimentary and defensive reinforcement were compared. Twelve dogs in the alimentary study were trained on a 50 percent partial reinforcement schedule, and 24 dogs were trained to avoid shock with either continuous shock availability and response contingent CS termination or with only 50 percent partial shock availability and response independent CS termination. One third of the subjects received bilateral medial prefrontal lesions, 12 dogs were given bilateral lesions of the lateral prefrontal cortex and the remaining subjects served as nonoperated controls. Generalization along the frequency dimension of the tonal CS was assessed during a sampling procedure within normal acquisition training, during complete extinction and following differentiation training. The results indicate specific effects from both the quality and the contingency of reinforcement. Within the limits of each reinforcement treatment, a dissociation occurred such that medial subjects tended to show heightened sensitivity to reinforcement density, while lateral subjects showed characteristic elevated reactivity during all generalization tests.

Animals↗

Intravenous self-administration of cathinone by rats.

Cathinone is the principal psychoactive constituent in leaves of the khat shrub. In some parts of the world, khat leaves are commonly chewed for their stimulant effects. While it has been demonstrated that rhesus monkeys will self-administer cathinone, there has been no demonstration of cathinone self-administration in rats. Two experiments were therefore conducted on rats fitted with intravenous catheters. On an FR 1 reinforcement schedule, the dose response curve for cathinone was shifted to the left of that for cocaine by a factor of approximately two. Within the sessions, cocaine infusions tended to be spaced evenly, whereas cathinone infusions were generally more frequent in the early portions of the session than later. In a second experiment, pretreatment with the dopamine D1-type receptor antagonist SCH 23390, at 10mg/kg, significantly increased the number of infusions obtained. Pretreatment with the D2-type receptor antagonist spiperone caused only a slight, non-significant increase in cathinone self-administration. These results demonstrate that cathinone is a potent reinforcer in rats and suggest a role for D1-type dopamine receptors in mediating its reinforcing effects.

Journal Article↗

Predictable individual differences in the initiation of cocaine self-administration by rats under extended-access conditions are dose-dependent.

RATIONALE: The characterization of self-administration (SA) under extended access conditions is necessary for the development of addiction models. OBJECTIVE: The purposes of this experiment were to investigate: (1) dose effects on the initiation of cocaine SA under extended access conditions; (2) predictable individual differences in SA under these conditions and their relationships to neuroendocrine function and cocaine dose. METHODS: After they were tested for their locomotor responses to novelty and to cocaine and trained to lever-press under a food-reinforced schedule, male Sprague-Dawley rats were allowed to SA cocaine (0.25, 0.5, 1.0, or 2.0 mg/kg per infusion, IV) by lever-pressing under a FR1 schedule during five consecutive daily 10-h sessions. Plasma corticosterone (CORT) and prolactin (PRL) were measured throughout the experiment. RESULTS: Rats tested at higher cocaine doses more readily acquired and showed increased drug intake and more regular patterns of SA. High responders (HR) to novelty self-administered greater amounts of cocaine, acquired more rapidly and displayed more regular SA compared to LR rats, but only at the lowest cocaine dose tested (i.e., 0.25 mg/kg per infusion). HR rats also exhibited a greater high-dose escalation of SA compared to LR rats. Novelty-induced (but not cocaine-induced) locomotor activity, pre-SA plasma CORT, and pre-SA food-reinforced lever-pressing predicted SA, but only at the lowest cocaine dose tested. No differences in plasma CORT or PRL were observed between LR and HR rats. CONCLUSIONS: The present findings indicate that predictable individual differences in cocaine SA under extended access conditions are relevant only at low doses and are surmountable by increasing the available dose of cocaine.

Animals↗

Hippocampal rhythmical slow activity during instrumental responses with sexual reinforcement in male rats.

The hippocampal EEG activity was recorded in male rats during the response-contingent reinforcement of a female. The instrumental response was a bar-pressing on a fixed-ratio-10 reinforcement schedule. The frequency of bar-pressing tends to increase during the succeeding copulatory series. The similar phenomenon was observed in the frequency of the hippocampal slow activity (RSA) accompanying the bar-pressing and the pursuit of the female. This tendency was most conspicuously present during the first copulatory series but became less evident during the following ones.

Animals↗

Ethanol-reinforced responding of naive rhesus monkeys: acquisition without induction procedures.

Rodents will typically consume greater amounts of low concentration ethanol (1-6%) than water. However, few primate oral self-administration studies have examined low ethanol concentrations. Additionally, there is a scarcity of data showing ethanol-maintained behavior without using induction procedures in either rats or primates. In this study, 14, free-feeding, naive, adult, male rhesus monkeys were given access to a 2% (w/v) ethanol solution and vehicle (tap water) during daily 3-hour sessions. Water was freely available between sessions. Liquids were available under a concurrent fixed-ratio four reinforcement schedule; thus, four responses (mouth-spout contacts) on either spout were immediately followed by the delivery of approximately 0.65 ml of liquid. In phase 1, tap water was available from both spouts. In phase 2, vehicle and a 2% ethanol solution were concurrently available. The 2% ethanol solution maintained considerably higher response rates than vehicle for 12 of 14 monkeys. In phase 3, food intake was limited. During this phase, the 2% ethanol solution maintained significantly higher response rates than vehicle for all monkeys. Additionally, during phase 3, ethanol intakes were greater than those in phase 2 for all monkeys. Central drug effects and taste factors are discussed. These results demonstrate that ethanol will serve as a reinforcer for naive rhesus monkeys in the absence of induction procedures.

Alcohol Drinking↗

Behavioral intervention to reduce water intake in the syndrome of psychosis, intermittent hyponatremia, and polydipsia.

We describe a non-intensive behavioral intervention using an A-B design with extended follow-up on an open psychiatric unit to reduce water intake in a 52-year-old man with the syndrome of psychosis, intermittent hyponatremia, and polydipsia. A reinforcement schedule contingent upon weight gain secondary to water intake was employed. Mean diurnal weight gain was 7.1 pounds during a 23-week baseline which dropped to 4.1 pounds following 23 weeks of treatment and at a 1-year follow-up. Estimated fluid consumption dropped from 10 liters to 4 liters daily and incidents of hyponatremia decreased by 62%.

Behavior Therapy↗

The effects of repeated treatment with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on the lever press responding of the rat under FI and DRL schedules of food reinforcement.

In general, the effects of 8-OH-DPAT on the body temperature of rats or in inducing the 5-HT syndrome show rapid tolerance. However, in contrast, the 8-OH-DPAT-induced increase in the activity of rats in a two-way active avoidance task only occurs after repeated administration, i.e. there is sensitisation. The present study was conducted to examine whether this developing hyperactivity may also be expressed as increased rates of lever press responding, and if so, under which conditions it occurs. Rats were trained to press levers under fixed interval 60-s (FI 60) or differential reinforcement of low rates 20-s or 72-s (DRL20, DRL72) schedules of food reinforcement. Groups of trained rats were then treated daily 5 min before testing with doses of 0.01, 0.1 and 1.0 mg/kg 8-OH-DPAT SC for 10-21 days. In all three procedures, in the first couple of days of drug treatment, 8-OH-DPAT generally suppressed lever pressing in a dose-dependent manner. Thereafter, tolerance to this effect was seen to a greater (DRL20, DRL72) or lesser (FI60) extent. Some evidence for stimulation of low rates of lever press responding was seen after 10 days treatment under FI60, but not in DRL20 or DRL72 during short 30 to 60 min long daytime tests although in the latter case, the rats responded to the stimulating effects of 0.8 mg/kg SC amphetamine administered once at the end of the experiment. However, when rats were allowed to respond under DRL72 testing for 12 h during the night, after 10 days treatment a clear stimulation of lever pressing was observed. This stimulation was not specific to lever pressing, however, since a stimulation of entries into the food tray and licking were also seen. From these results, it may be concluded that the stimulating effect of 8-OH-DPAT after repeated administration may be expressed as increased rates of lever pressing, but not under all conditions in which psychomotor stimulation by amphetamine is seen. The potential for 8-OH-DPAT and related compounds to stimulate motor responding in this way should be taken into account when interpreting the effects of these drugs in animal models of psychiatric disorders.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Reversal of a postnatal alcohol-induced deficit in learned persistence in the rat by d-amphetamine.

Periodic (high peak) exposure to alcohol during early infancy in the rat has been shown to disrupt the partial reinforcement extinction effect (PREE), a measure of persistence learning, when rats were tested at weaning age. The current study examined the effects of d-amphetamine (0.3 mg/kg, i.p.) on the PREE after early postnatal exposure to alcohol (4.5 mg/kg) delivered in a milk-based diet or an isocaloric control diet via oral intubation once a day on postnatal days 4 to 9. On postnatal days 20 and 21, rats were trained on either a continuously reinforced or partially reinforced schedule of food reward, followed by extinction. Rats were randomly assigned to eight conditions, depending on diet, drug, and reward schedule. The results were (1) a replication of the finding that periodic (high peak) exposure to alcohol diminishes the PREE, and (2) that amphetamine restores the PREE to normal levels in alcohol-treated animals, and may reduce the PREE in control subjects. The possible role of noradrenergic and dopaminergic systems in situations of extinction and nonreward are discussed.

Animals↗

Duration, response, and location: the influence of upcoming 32% sucrose on rats' licking or lever pressing for 1% liquid sucrose.

The present study investigated whether rats' rates of licking or pressing a lever for 1% liquid sucrose delivered by a continuous reinforcement schedule would decrease (contrast) or increase (induction) when the upcoming period would allow access to 32% sucrose and whether such changes would be influenced by how long each substance was available. In Experiment 1, different groups of rats licked a spout or pressed a lever for 1% sucrose in the first half of the session and, in different conditions, for 1% or 32% sucrose in the second half. Across conditions, halves of the session were 3, 6, 12, or 24 min long. Upcoming 32% sucrose significantly decreased rates of licking at each duration whereas it increased rates of lever pressing except when access duration was 3 min. Experiment 2 replicated Experiment 1 with the exception that rats that licked did so from the same spout in both halves of the session and rats that pressed a lever collected the sucrose reinforcers in the different halves at different locations. In these procedures, upcoming 32% sucrose significantly increased rates of licking. Significant, but small, increases in rates of lever pressing were still observed. The present results suggest that continuous reinforcement or duration of access to sucrose are not primary determinants of whether contrast or induction is observed. Rather, they suggest that the type of behavior (licking versus pressing a lever) and the location at which the substances are collected and consumed play a large role in which effect occurs.

Animals↗

Effects of quinpirole on behavioral extinction.

Behavioral effects of quinpirole (QNP), a dopamine D(2) receptor agonist, suggest it impacts neural mechanisms mediating goal-directed behaviors, as well as behavioral extinction following removal of a primary reinforcer. The present study investigated the effect of QNP on behavioral extinction following the omission of contingent reinforcement, and whether this effect is related to acquisition or processes specific to extinction. Rats were trained on a continuous reinforcement schedule to nose-poke for water reward. Using a free-operant procedure, rats completed approximately 70 responses for each of four consecutive days. On the fifth day reward was withheld. Rats were assigned to one of five groups in which they received 0.3 mg/kg QNP ip either during the first day (acquisition phase), the second 2 days (maintenance phase), the last day (extinction phase), or during all days. A fifth group received vehicle injections. Rats receiving QNP during the acquisition and maintenance phase did not differ significantly from the control group during the extinction phase, although they demonstrated reduced response rates on days they received QNP. However, rats treated during the extinction phase or during all phases demonstrated a significant reduction in the rate of extinction. This effect cannot be attributed to an increase in general behavioral arousal because response rates for reinforced responses did not differ significantly among groups following acquisition of the behavior. The reduced extinction effect does not appear to be related to abnormalities in the initial behavior-reward association, but instead may result from enhanced engagement of learned behavioral patterns, or from interference of signals associated with removal of predicted reinforcement.

Analysis of Variance↗

Amsel's frustration effect: a pavlovian replication with control for frequency and distribution of rewards.

Amsel's frustration effect refers to a facilitation of behavior immediately after unexpected nonreward. The original experiments were plagued with problems of interpretation, mainly because the critical comparison involved conditions that were not equated in terms of reward frequency and amount. A replication of the original experiment (with a 50% partial reinforcement schedule used to induce response facilitation) is reported here with one important addition: A control group matched in terms of reward parameters, for which the reward was not signaled by a discrete cue. Matching is achieved through the use of a Pavlovian training procedure. The results show facilitation of rats' lever-contact performance after unexpected reward omissions. The control group showed no facilitation. These results provide support for the view that response facilitation is caused by increased arousal after unexpected nonreward.

Animals↗