Review. Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex

Abstract

Binge drinking is an increasingly recognized problem within the UK. We have studied the relationship of binge drinking to cognitive and emotional functioning in young adults, and have found evidence for increased impulsivity, impairments in spatial working memory and impaired emotional learning. Since in human studies it is difficult to understand whether such behavioural changes pre-date or are a consequence of binge drinking, we have also studied parallel behaviours in a rodent model, in which rats are exposed to intermittent episodes of alcohol consumption and withdrawal. In this model, and in parallel with our findings in human binge drinkers, and alcoholic patients who have undergone multiple episodes of detoxification, we have found evidence for impairments in aversive conditioning as well as increased impulsivity. These behavioural changes are accompanied by facilitated excitatory neurotransmission and reduced plasticity (long-term potentiation (LTP)) in amygdala and hippocampus. The impaired LTP is accompanied by both impaired associative learning and inappropriate generalization of previously learned associations to irrelevant stimuli. We propose that repeated episodes of withdrawal from alcohol induce aberrant neuronal plasticity that results in altered cognitive and emotional competences.

Figure 1

Conditioned fear in (a) alcoholic patients and their control counterparts and (b) human bingeing and non-bingeing social drinkers; groups were matched for age, gender and verbal IQ. Electromyographic activity of the orbicularis oculi muscle (EMG) to an aversive white noise (97 dB) in the presence of an auditory CS+ (filled bars) and CS− (open bars) stimulus of the same intensity (63 dB) but different frequency (900 or 1700 Hz). During training sessions, CS+ was followed by aversive white noise (US) and CS− by nothing. Testing took place in the presence of CS stimuli without reinforcement (test of CS effects) and also when each stimulus (CS+ and CS−) was followed by the white noise startle stimulus (test of CS-induced potentiation of startle). A group×stimulus interaction was found in the comparison between bingers and non-bingers and also between alcoholic patients and controls (F_2,32=6.98; p=0.003 and F_2,48=4.31; p=0.02, respectively). This interaction was attributable to a higher response to the CS+ compared with the CS− in non-binger and control groups, but not in binger and alcoholic patient groups.

Figure 2

(a) The aberrant plasticity model of withdrawal-induced deficits in associative conditioning. Prior to learning, activation of synapse FS as a consequence of footshock-induced activity in somatosensory systems leads to activation of an output neuron giving rise to a fear response. Activation of an auditory neuron by tone A is unable to gain access to the output neuron subserving the fear response, as synapse A is ‘silent’ at this stage. During associative learning, if the neuron carrying information about tone A (CS+) is active at the same time as the neuron carrying information regarding the footshock, then as a result of activation of the synapse FS, local depolarization will occur, allowing activity at synapse A also to induce depolarization in the postsynaptic membrane. Consequently, synapse A will be strengthened, so that the activation of the tone A pathway will now gain access to the output pathway, i.e. associative conditioning has occurred. Synapse B remains silent as it is never activated at the same time as synapse FS. However, if alcohol withdrawal induces activation of synapse B as well as of synapse FS, then synapse B should also be strengthened, so that tone B might now gain access to the output pathway, even though it has never been paired with footshock. Furthermore, if withdrawal-induced synaptic strengthening occurs prior to conditioning, then synapse A will already have been strengthened, and will no longer be available for conditioning. (b) Suppression ratios (a measure of conditioned fear) in RWD rats (squares), given the same exposure to alcohol, but only a SWD (filled circles), or rats fed a non-alcohol control diet (CON (open circles)). The rats were trained prior to alcohol treatment to associate a tone CS+ with footshock, so that the CS+ caused a suppression of behaviour (giving suppression ratio values less than 0.5). The CS− was an alternative tone signal, that did not predict shock, and which therefore did not suppress behaviour (giving a suppression ratio of approx. 0.5). Two weeks following the final day of alcohol treatment, the rats were once again presented with the CS+, as well as the CS−, and a novel tone, intermediate between the CS+ and the CS−. The SWD and control rats continued to show suppression to the CS+, but not to the CS−, with an intermediate degree of suppression to the novel tone. By contrast, the RWD rats showed equal suppression to all three tones (adapted from Stephens et al. 2005).