The reinforcing action of morphine and its paradoxical side effect

Rats were trained to run down a runway for food in the goal box, and were then tested with one trial per day for 5 days. After running in the runway and eating in the goal box each rat was injected with a drug and returned to the empty goal box for 50 min. Over the 5 trials, rats that received morphine sulphate increased their running speed approximately 400% while the amount of food they ate in the goal box decreased to about 70% of baseline values. The running speed of rats that received lithium chloride decreased to about 30%, while the amount of food they ate decreased to less than 10% of baseline. These two variables did not change for rats that received saline injections. The large increases in running speed observed in the rats that received morphine injections were attributed to an interaction (but not simple summation) between the positive reinforcing effects of morphine and food. The accompanying paradoxical decrease in amount eaten was discussed in terms of the complex pharmacological properties of morphine and it was suggested that morphine may have a reinforcing effect on behavior that is independent of its affective properties.     

Topographic analysis of areas of negative and positive reinforcement in the central grey matter of the rat (author's transl)

Utilization of a movable electrode has permitted an analysis of areas of negative reinforcement (switch-off response) and areas of positive reinforcement (self-stimulation responses), as well as the behavioral effects of a simultaneous activation of systems of negative and positive reinforcement at the ambivalent sites of a junction-area. Within the areas of reinforcement, gradients were uncovered in the rates of both switch-off and self-stimulation responses.     

Morphine dependence in rats: Secondary reinforcement from environmental stimuli

Rats which were physically dependent on morphine were repeatedly placed in distinctive environments immediately after being injected with their daily dose of the drug (120 mg/kg). The effects of morphine, e.g. reduction of withdrawal symptoms, were thus associated with particular environmental stimuli and when the rats were tested in withdrawal, they preferred these environments to unfamiliar neutral ones. They also tended to have higher photocell activity scores during these tests. Avoidance of such environments was not shown by rats which had repeatedly been placed in them when in states of withdrawal.     

Two sides of the same coin: learning via positive and negative reinforcers in the human striatum

The human striatum has been previously implicated in the processing of positive reinforcement, but less is known about its role in processing negative reinforcement. In this experiment, participants learn specific approach or avoidance responses, mediated by positive and negative reinforcers respectively to investigate how affective learning and associated neural activity are influenced by the motivational context in which learning occurs. The paradigm was divided into two discrete sessions, where participants could either earn monetary rewards (approach sessions) or avoid monetary losses (avoid sessions) based on successful learning. Specifically, a conditioned cue predicted the chance to win or avoid losing money contingent on a correct button press (pre-learning trials), which upon learning led to the delivery of rewards or termination of losses (post-learning trials). Skin conductance responses (SCRs) and subjective ratings confirmed a learning effect (greater SCRs pre vs. post-learning) irrespective of reinforcer valence. Concurrently, activity in the ventral striatum was characterized by a similar learning effect, with greater responses during pre-learning. Interestingly, such learning effect was enhanced in the presence of a negative reinforcer, as suggested by an interaction between learning phase and session, highlighting the influence negative reinforcers can have on striatal circuits involved in learning and motivated behavior.     

Anxiety and feedback negativity

It has been suggested that anxious individuals are more prone to feel that negative outcomes are particularly extreme and to interpret ambiguous outcomes as negative compared to nonanxious individuals. Previous studies have demonstrated that the feedback negativity (FN) component of event‐related brain potential (ERP) is sensitive to outcome evaluation and outcome expectancy. Hence, we predicted that the FN should be different between high trait‐anxiety (HTA) and low trait‐anxiety (LTA) individuals. To test our hypothesis, the ERPs were recorded during a simple monetary gambling task. The FN was measured as a difference wave created across conditions. We found that the amplitude of the FN indicating negative versus positive outcomes was significantly larger for LTA individuals compared to HTA individuals. However, there was no significant difference in the FN between groups in response to ambiguous versus positive outcomes. The results indicate that there is a relationship between the FN and individual differences in anxiety. We suggest that these results reflect the impact of anxiety on outcome expectation. Our results challenge the reinforcement learning theory of error‐related negativity, which proposes that ERN and FN reflect the same cognitive process.     

Response to Westlund's commentary: ‘Can conditioned reinforcers and variable-Ratio Schedules make food- and fluid control redundant?’

In this short communication, we respond to Westlund's critique of the NC3Rs Working Group report on refinement of the use of food and fluid control as motivational tools for macaques used in behavioural neuroscience research. The suggestions Westlund makes - in particular, the use of conditioned reinforcers and variable ratio schedules - were considered by the Working Group but were not included in the report as specific recommendations. We outline the reasons for this and also address some misunderstandings of our position.     

The orbitofrontal cortex: Neuronal activity in the behaving monkey

Summary Single unit recording of neurons in the orbitofrontal cortex of the alert rhesus monkey was used to investigate responses to sensory stimulation. 32.4% of the neurons had visual responses that had typical latencies of 100–200 ms, and 9.4% responded to gustatory inputs. Most neurons were selective, in that they responded consistently to some stimuli such as foods or aversive objects, but not to others. In a number of cases the neurons responded selectively to particular foods or aversive stimuli. However, this high selectivity could not be explained by simple sensory features of the stimulus, since the responses of some neurons could be readily reversed if the meaning of the stimulus (i.e. whether it was food or aversive) was changed, even though its physical appearance remained identical. Further, some bimodal neurons received convergent visual and gustatory inputs, with matching selectivity for the same stimulus in both modalities, again suggesting that an explanation in terms of simple sensory features is inadequate.Neurons were also studied during the performance of tasks known to be disrupted by orbitofrontal lesions, including a go/no go visual discrimination task and its reversal. 8.6% of neurons had differential responses to the two discriminative stimuli in the task, one of which indicated that reward was available and the other saline. Reversing the meaning of the two stimuli showed that whereas some differential units were closely linked to the sensory features of the stimuli, and some to their behavioural significance, others were conditional, in that they would only respond if a particular stimulus was present, and if it was the one being currently rewarded. Other neurons had activity related to the outcome of the animal's response, with some indicating that reinforcement had been received and others, that an error had been made and that a reversal was required.Thus, neurons in the orbitofrontal cortex possess highly coded information about which stimuli are present, as well as information about the consequences of the animal's own responses. It is suggested that together they may constitute a neuronal mechanism for determining whether particular visual stimuli continue to be associated with reinforcement, as well as providing for the modification of the animal's behavioural responses to such stimuli when those responses are no longer appropriate.     

Airlicking vs. water drinking in a T-maze: Thirsty rats prefer water

This study compares the reinforcement values of drinking and airlicking in thirsty rats. What duration of airlicking is equivalent in reward value to 10 sec of drinking? Water-deprived rats were trained to lick an airstream from a standard drinking tube. They were then tested in a T-maze in which they were confronted with a choice between 10 sec of water and access to an airstream for periods of airlicking varying from 40–300 sec. All of the rats preferred the water to the airstream, regardless of the duration of the airlicking reward and irrespective of the goal positions in the maze. It is concluded that for a thirsty rat the rewarding effects of drinking water are very much greater than those of airlicking.     

强力纤维强化树脂夹板固定下颌前牙的临床观察

目的　探讨强力纤维强化树脂夹板固定下颌前牙的临床效果。方法　应用强力纤维强化树脂夹板 ,对 15例慢性牙周炎患者的Ⅲ°松动的下前牙进行固定 ,观察固定后 6个月牙周探诊深度 (probingdepth ,PD)、附着丧失 (attachmentloss ,AL)和根尖片的变化。结果　患牙的PD由 5 .5 9mm减至 5 .0 6mm ,AL由 3.96mm减至 2 .84mm ,临床状况明显改善 (P <0 .0 0 1)。所有患牙均无进一步的骨破坏 ,其中 3例患者的骨破坏有明显改善。结论应用强力纤维强化树脂夹板固定下颌前牙可获得较满意的临床效果。