The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat.

AMPA receptor potentiators enhance AMPA receptor-mediated glutamatergic neurotransmission and may have therapeutic potential as cognitive enhancers or antidepressants. The anatomical basis for the action of AMPA receptor potentiators is unknown. The aim of this study was to determine the effects of the biarylpropylsulfonamide AMPA receptor potentiator, LY404187 (0.05 to 5 mg/kg subcutaneously), upon cerebral glucose utilization and c-fos expression using 14C-2-deoxglucose autoradiography and c-fos immunocytochemistry. LY404187 (0.5 mg/kg) produced significant elevations in glucose utilization in 28 of the 52 anatomical regions analyzed, which included rostral neocortical areas and the hippocampus, as well the dorsal raphe nucleus, lateral habenula, and locus coeruleus. No significant decreases in glucose utilization were observed in any region after LY404187 administration. The increases in glucose utilization with LY404187 (0.5 mg/kg) were blocked by pretreatment with the AMPA receptor antagonist LY293558 (25 mg/kg), indicating that LY404187 acts through AMPA receptor-mediated mechanisms. LY404187 (0.5 mg/kg) also produced increases in c-fos immunoreactivity in the cortex, locus coeruleus, and the dorsal raphe nucleus. These studies demonstrate neuronal activation in key brain areas that are associated with memory processes and thus provide an anatomical basis for the cognitive enhancing effects of AMPA receptor potentiators.     

The contribution of optimism and quality of life to depression in an acute coronary syndrome population.

BACKGROUND: Numerous longitudinal studies have revealed that depression following an acute cardiac event poses a risk factor for poor cardiac outcomes. It is therefore important to identify modifiable predictors of depression in order to develop a variety of interventions with this population. AIMS: The aim of the present research was to determine whether the relationship between optimism and depressive symptoms was mediated by self-reported quality of life (QOL) in acute coronary syndrome patients. METHODS: Two weeks following hospital discharge (Time 1) 59 participants completed a self-report questionnaire. Four weeks later (Time 2), 49 of these participants completed the same questionnaire. RESULTS: At Time 1, the relationship between optimism and depressive symptoms was partially mediated by functional QOL and symptom QOL. Furthermore, the relationship between Time 1 optimism and Time 2 depressive symptoms was partially mediated by Time 1 functional QOL. When each of the Time 1 variables were used to predict Time 2 depressive symptoms, only optimism continued to predict depressive symptoms over and above the influence of Time 1 depressive symptoms and other covariates. CONCLUSION: These findings suggest the underlying importance of optimism in influencing depressive symptoms in acute coronary syndrome patients, and indicate that optimism and perceptions of functional QOL may be a possible rehabilitation target for this population.     

Predictors of Partner Notification for C. trachomatis and N. gonorrhoeae: An Examination of Social Cognitive and Psychological Factors

Efforts to control chlamydial and gonococcal infections include notifying eligible sexual partners of possible infection, primarily by asking the diagnosed patient to notify their partners. This approach, known as patient referral, is widely used but poorly understood. The current study examined psychosocial and cognitive factors associated with patient referral among an urban, minority sample of 168 participants recently diagnosed with Chlamydia trachomatis or Neisseria gonorrhoeae. At a follow-up interview 1-month from diagnosis, participants were more likely to have notified all eligible partners if they had greater intention to notify at baseline (OR = 3.72; 95% CI = 1.34, 10.30) and if they had only one partner at baseline (OR = 4.08; 95% CI = 1.61, 10.31). There were also gender differences as well as differences based on type of partner (i.e., regular, casual, one-time). The implications of these findings for the design of programs to promote patient referral for sexually transmitted infections are discussed. Schwartz, Malka, Augenbraun, McCormack, and Wilson are with the State University of New York, Downstate Medical Center, Brooklyn, NY, USA; Rubin is with the New York City Department of Health, Bureau of STD Control, New York, NY, USA; Rubin, Hogben, and Liddon are with the Centers for Disease Control and Prevention, Atlanta, GA, USA; Schwartz is with the Department of Preventive Medicine and Community Health, SUNY Downstate Medical Center, Box 1240, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.     

Intracortical inhibition in the human trigeminal motor system.

OBJECTIVE: To investigate the presence and features of short-interval intracortical inhibition (SICI) in the human trigeminal motor system. METHODS: Surface electromyogram (EMG) was recorded from left and right digastric muscles in 7 subjects, along with additional experiments with intramuscular EMG in 2 subjects. Focal transcranial magnetic stimulation (TMS) was used to activate the motor cortex of one hemisphere and elicit motor evoked potentials (MEPs) in digastric muscles on each side, at rest and while subjects activated the muscles at 10% maximal EMG. Paired or single TMS pulses were delivered in blocks of trials, while conditioning TMS intensity and interstimulus interval (ISI) were varied. RESULTS: At rest, paired TMS (3-ms ISI) with conditioning intensities 0.8-0.9x active motor threshold (TA) reduced the digastric MEP amplitude to a similar extent bilaterally. Conditioning at 0.5-0.7TA did not significantly reduce the MEP. MEP amplitude was reduced to a similar extent in both digastric muscles by ISIs between 1 and 4 ms (0.8TA). Voluntary bilateral activation of digastric muscles reduced the effectiveness of conditioning TMS compared to the resting state, with no differences between sides. The similarity of the responses in both digastric muscles was not due to EMG cross-talk (estimated to be approximately 10% in surface records and approximately 2% in intramuscular records), as the intramuscular records showed the same pattern as the surface records. CONCLUSIONS: The effects of paired-pulse TMS on digastric are similar to those reported for contralateral hand muscles, and are consistent with activation of SICI circuits in M1 by conditioning TMS. Our evidence further suggests that the corticomotor representations of left and right digastric muscles in M1 of a single hemisphere receive analogous inhibitory modulation from SICI circuits. SIGNIFICANCE: SICI has been demonstrated in the face area of motor cortex controlling the trigeminal motor system in normal subjects. This method can be used to investigate abnormalities of SICI in movement disorders affecting the masticatory muscles in humans.     

Reciprocal axo-axonal synapses between the common inhibitor and excitor motoneurons in crustacean limb muscles

Summary Nerve terminals of the common inhibitor motoneuron in a crab (Eriphia spinifrons) limb closer muscle and in a crayfish (Procambarus clarkii) limb accessory flexor muscle make neuromuscular synapses with the muscle membrane (postsynaptic inhibition) as well as axo-axonal synapses with the terminals of the excitatory axon (presynaptic inhibition). That transmission is from the inhibitor to the excitor terminals at these axo-axonal synapses is indicated by the occurrence on the inhibitor membrane of presynaptic dense bars denoting sites of transmitter release. Axo-axonal synapses with the opposite polarity, in which transmission is from an excitatory onto an inhibitory terminal, were occasionally seen either adjacent to or separate from the inhibitory axo-axonal synapse. Nerve terminals of the specific inhibitor in the crayfish opener muscle were seen to make numerous axo-axonal output synapses upon excitatory nerve terminals but excitor nerve terminals were not seen to make output synapses onto inhibitor terminals. Thus reciprocal axo-axonal synapses appear to be a feature of the common inhibitor but not of the specific inhibitor. The excitor-to-inhibitor component of these reciprocal synapses may serve to limit transmitter output in the common inhibitor axon by activating glutamate_B receptors which facilitate efflux of K⁺ and hyperpolarization of the membrane.