The current study assessed the normal development of cortical auditory evoked potentials (CAEPs) in humans presented with pure tone stimuli at relatively fast stimulus rates. Traditionally, maturation of sound processing indexed by CAEPs has been studied in paradigms using inter-stimulus intervals (ISIs) generally slower than 1 Hz. While long ISIs may enhance the amplitude of CAEP components, speech information generally occurs at more rapid rates. These slower rates of sound presentation may not accurately assess auditory cortical functions in more realistic sound environments. We examined the effect of temporal rate on the elicitation of the P1-N1-P2-N2 components to unattended sounds at four levels of stimulus onset asynchrony (SOA, onset to onset, 200, 400, 600, and 800 ms) in children grouped separately by year (ages 8, 9, 10, 11 years), in adolescents (age 16 years) and in one group of young adults (ages 22-40 years). We found that both age and stimulus rate produced profound changes in CAEP morphology. Between the ages of 8-11 years, the P1 and N2 components dominated the ERP waveform at all stimulus rates. N1, the dominant CAEP component in adults, appeared as a bifurcation in a broad positive peak at earlier ages, and did not emerge as a separate component until adolescence. While the P1-N1-P2 components are more "adult-like" than "child-like" in the adolescent subjects, the N2 component, a hallmark of the child obligatory response, was still present. Faster rates resulted in the suppression of discrete components such that by 200 ms, only P1 in the adults and adolescents, and both P1 and N2 in the youngest children were discernable. We conclude that both age and ISI are important variables in the assessment of auditory cortex function and maturation. The presence of N2 in adolescents indicates that auditory cortical maturation persists into teen years.

Hemopressin (Hp), a 9-residue alpha-hemoglobin-derived peptide, was previously reported to function as a CB(1) cannabinoid receptor antagonist (1) . In this study, we report that mass spectrometry (MS) data from peptidomics analyses of mouse brain extracts identified N-terminally extended forms of Hp containing either three (RVD-Hpalpha) or two (VD-Hpalpha) additional amino acids, as well as a beta-hemoglobin-derived peptide with sequence similarity to that of hemopressin (VD-Hpbeta). Characterization of the alpha-hemoglobin-derived peptides using binding and functional assays shows that in contrast to Hp, which functions as a CB(1) cannabinoid receptor antagonist, both RVD-Hpalpha and VD-Hpalpha function as agonists. Studies examining the increase in the phosphorylation of ERK1/2 levels or release of intracellular Ca(2+) indicate that these peptides activate a signal transduction pathway distinct from that activated by the endocannabinoid, 2-arachidonoylglycerol, or the classic CB(1) agonist, Hu-210. This finding suggests an additional mode of regulation of endogenous cannabinoid receptor activity. Taken together, these results suggest that the CB(1) receptor is involved in the integration of signals from both lipid- and peptide-derived signaling molecules.