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Rationale: Noradrenergic processes within the amygdala have been implicated in the modulation of memory for emotional material. The amygdala has also been associated with the processing of facial expressions of emotion, particularly those of fear and sadness. However, the role of noradrenaline in the latter process is unknown., Objective: Therefore the present study examined the effect of an oral beta-blocker (propranolol, 80 mg) upon facial expression recognition in healthy volunteers., Methods: Facial expressions of six basic emotions, which had been "morphed" between neutral and each emotional standard, were used in the recognition task. Subjects completed this task both before and 1 h following either propranolol or a placebo. Control measures of choice reaction time and vigilance performance were also included to assess any non-specific effects of the drug upon alertness and speed., Results: The administration of propranolol, relative to placebo, specifically increased reaction time to identify facial expressions of sadness correctly, in the absence of changes in speed to recognise other facial expressions of emotion. Subjective ratings of mood and alertness as well as speed in the two control tasks were not altered by propranolol, arguing against an account in terms of general sedation., Conclusions: These data suggest that noradrenergic processes are not only involved in memory for emotional material but also in the evaluation of sadness from facial expression. The selective nature of this effect adds to evidence suggesting that the recognition of different expressions of emotion depends upon at least partly separable neural processes. A role for noradrenaline in recognising sadness in others has potential relevance for our understanding of disorders characterised by disturbances in emotional processing.

Rationale: Tyrosine depletion has been shown to reduce dopamine over activity in animal and human investigations. However, the effects on basal dopamine function have not been explored. Such information could establish tyrosine depletion as an effective probe of dopamine function in healthy volunteers and would also have relevance for future therapeutic applications of this manipulation., Objective: The present study investigated the effect of acute tyrosine depletion on dopamine function in healthy volunteers using a combination of neuroendocrine, neuropsychological and subjective measures., Methods: On one occasion, volunteers received an amino acid drink selectively lacking tyrosine and phenylalanine (TYR-free), whilst on the other they received a balanced (BAL) amino acid drink. Plasma prolactin, amino acid levels and subjective state were monitored over 6 h following the two drinks, and volunteers also completed a battery of tests from the CANTAB, including measures of spatial memory previously found to be sensitive to changes in dopamine function., Results: Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, indicative of decreased dopamine neurotransmission within the hypothalamus. Following the TYR-free drink, volunteers were impaired at spatial recognition memory and spatial working memory. Volunteers also tended to report that they felt less good following the TYR-free than the BAL mixture., Conclusion: Tyrosine depletion in healthy volunteers affected baseline dopamine function on the different measures employed in this study. Tyrosine depletion would thereby seem valuable as a probe of dopamine function in human volunteers. Ratings of depression and other aspects of cognitive function were unaffected, suggesting that this manipulation may be free of significant side effects when used as a treatment for conditions characterised by dopamine over activity, such as acute mania and schizophrenia.

We have shown that prior repeated exposure to d-amphetamine facilitates appetitive Pavlovian conditioning. However, animals sensitised in this manner also show elevated levels of stimulated activity. To investigate whether enhanced conditioning was dependent upon increased activity, a conditioned inhibition task was employed in the present study. Rats received d-amphetamine (2 mg/kg, i.p.) or vehicle once per day for 7 days. After a 7-day drug-free period, an activity assay confirmed that repeated d-amphetamine treatment markedly elevated the locomotor response to a subsequent challenge with 0.5 mg/kg d-amphetamine. Conditioning began 6 days later. In phase 1, stimulus A+ (light or tone) immediately preceded sucrose availability (excitatory conditioning). In phase 2, sucrose again was presented after A+ alone, but not after presentation of a compound of A+ with a second stimulus (AB-). Sensitisation enhanced the acquisition of conditioned approach behaviour to the excitatory stimulus A+ in phase 1. Furthermore, acquisition of conditioned inhibition to the stimulus compound, AB-, was also facilitated. Thus, sensitised rats showed reduced levels of responding to the stimulus compound far sooner than controls. Finally, a retardation test was carried out in stage 3, in which the inhibitory stimulus B- was paired alone with sucrose reward. Sensitised rats initially showed retarded acquisition of excitatory conditioned responding relative to controls, suggesting that B possessed stronger inhibitory associations in these animals. However, sensitised animals again exhibited higher levels of responding in later sessions, consistent with the enhanced excitatory conditioning shown in phase 1. These findings suggest that prior repeated d-amphetamine enhanced the acquisition of inhibitory and excitatory Pavlovian associations; a propensity not readily attributable to stimulated locomotor hyperactivity.

This study examined the role of the mesoamygdaloid dopamine projection in stimulus-reward learning. Bilateral post-session intra-amygdala microinjections of d-amphetamine were carried out in rats during training in a discriminative approach task known to be sensitive to experimental manipulations of the amygdala. The experiment consisted of two phases: discriminative approach training, and a subsequent assessment of instrumental conditioned reward efficacy. During discriminative approach training, subjects were trained to associate a neutral stimulus with 10% w/v sucrose reward. Each trial consisted of a 1-s light stimulus followed by a 5-s presentation of the sucrose reward. Approach behaviour into the recess housing sucrose reward was measured during each trial. Inappropriate approach behaviour (approach outside of the trial periods) was punished by delaying the next trial. Intra-amygdala d-amphetamine (10 microg/side) enhanced the rate of acquisition of discriminative approach behaviour. This effect was most evident early during training (sessions 2-4) and by the tenth session both groups had reached similar asymptotic performance. Horizontal and vertical activity increased slightly across sessions, but there was no indication of a differential effect of d-amphetamine. Thus, intra-amygdala microinjections of d-amphetamine enhanced selectively the acquisition of the stimulus-reward association. During a subsequent test of instrumental conditioned reward, presentation of the conditioned light stimulus was made contingent upon performance of a novel lever-pressing response (probability 0.5). Responding on a second, control lever was without programmed consequences. Sucrose reward was not available at any point, and subjects were tested drug-free. In both groups the conditioned stimulus was found to possess significant conditioned rewarding efficacy. Extraneous behaviour was increased in the d-amphetamine group but the rewarding properties of the conditioned stimulus were unaltered. These findings demonstrate that the mesoamygdaloid dopamine projection modulates the acquisition of a stimulus-reward association, but is apparently without subsequent effect on the rewarding efficacy of a conditioned stimulus.