Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner.

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here, we show that low-dose alcohol (0.6 g/kg/30 minutes) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared with behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol-reinforced but not sucrose-reinforced responding and was ineffective following intra-AcbC infusion. Because GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor myristolated autocamtide-2-related inhibitory peptide (m-AIP) dose-dependently reduced alcohol self-administration. A subthreshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction.

Toxigenic cutaneous diphtheria in a returned traveller.

Diphtheria is rarely reported in Australia. A case of cutaneous diphtheria was reported to the South Australian Department for Health and Ageing in April 2013 in an Australian-born 18-year-old female following travel in India. The case presented with a skin ulcer on her toe. Toxigenic Corynebacterium diphtheriae was isolated from a swab of the lesion. The case was treated with antibiotics. The public health response included infection control advice, assessing the case and household contacts for organism carriage and providing antimicrobial chemoprophylaxis to contacts. Although cutaneous diphtheria is not included as part of the Australian communicable disease surveillance case definition, this may be an oversight as international evidence demonstrates that it is a source of organism transmission and can potentially result in outbreaks among susceptible populations. This formed the rationale for the public health response to this particular case. The protocol for the public health management of diphtheria in South Australia has since been revised to include cutaneous lesions caused by the toxigenic strain of the organism as part of the surveillance case definition.

Postactivation depression and recovery of reflex transmission during repetitive electrical stimulation of the human tibial nerve.

H-reflexes are progressively depressed, relative to the first response, at stimulation frequencies above 0.1 Hz (postactivation depression; PAD). Presently, we investigated whether H-reflexes "recover" from this depression throughout 10-s trains of stimulation delivered at physiologically relevant frequencies (5-20 Hz) during functionally relevant tasks (sitting and standing) and contraction amplitudes [relaxed to 20% maximum voluntary contraction (MVC)]. When participants held a 10% MVC, reflex amplitudes did not change during 5-Hz stimulation. During stimulation at 10 Hz, reflexes were initially depressed by 43% but recovered completely by the end of the stimulation period. During 20-Hz stimulation, reflexes were depressed to 10% and recovered to 36% of the first response, respectively. This "postactivation depression and recovery" (PAD&R) of reflex amplitude was not different between sitting and standing. In contrast, PAD&R were strongly influenced by contraction amplitude. Reflexes were depressed to 10% of the first response during the relaxed condition (10-Hz stimulation) and showed no depression during a 20% MVC contraction. A partial recovery of reflex amplitude occurred when participants were relaxed and during contractions of 1-5% MVC. Surprisingly, reflexes could recover completely by the third pulse within a stimulation train when participants held a contraction between 5 and 10% MVC during stimulation at 10 Hz, a finding that challenges classical ideas regarding PAD mechanisms. Our results support the idea that there is an ongoing interplay between depression and facilitation when motoneurons receive trains of afferent input. This interplay depends strongly on the frequency of the afferent input and the magnitude of the background contraction but is relatively insensitive to changes in task.