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We previously reported that perineuronal nets (PNNs) are required for cocaine-associated memories. Perineuronal nets are extracellular matrix that primarily surrounds parvalbumin (PV)-containing, GABAergic fast-spiking interneurons (FSIs) in the medial prefrontal cortex (mPFC). Here we measured the impact of acute (1 d) or repeated (5 d) cocaine exposure on PNNs and PV cells within the prelimbic and infralimbic regions of the mPFC. Adult rats were exposed to 1 or 5 d of cocaine and stained for PNNs (using Wisteria floribunda agglutinin) and PV intensity 2 or 24 h later. In the prelimbic and infralimbic PFC, PNN staining intensity decreased 2 h after 1 d of cocaine exposure but increased after 5 d of cocaine exposure. Cocaine also produced changes in PV intensity, which generally lagged behind that of PNNs. In the prelimbic PFC, both 1 and 5 d of cocaine exposure increased GAD65/67 puncta near PNN-surrounded PV cells, with an increase in the GAD65/67-to-VGluT1 puncta ratio after 5 d of cocaine exposure. In the prelimbic PFC, slice electrophysiology studies in FSIs surrounded by PNNs revealed that both 1 and 5 d of cocaine exposure reduced the number of action potentials 2 h later. Synaptic changes demonstrated that 5 d of cocaine exposure increased the inhibition of FSIs, potentially reducing the inhibition of pyramidal neurons and contributing to their hyperexcitability during relapse behavior. These early and rapid responses to cocaine may alter the network stability of PV FSIs that partially mediate the persistent and chronic nature of drug addiction.

No abstract

The present studies represent the first published report of a dopamine D1 positive allosteric modulator (PAM). D1 receptors have been proposed as a therapeutic target for the treatment of cognitive deficits associated with schizophrenia. However, the clinical utility of orthosteric agonist compounds is limited by cardiovascular side effects, poor pharmacokinetics, lack of D1 selectivity, and an inverted dose response. A number of these challenges may be overcome by utilization of a selective D1 PAM. The current studies describe two chemically distinct selective for human and nonhuman primate D1 receptors, but lacks activity at the rodent (rat and mouse) D1 receptors. Using molecular biology techniques, a single amino acid was identified at position 130, which mediates the species selectivity of Compound B. These data represent the first described D1-selective PAMs and define critical amino acids that regulate species selectivity.

The dominating non-volatile taste compounds in commercial brewed soy sauces were determined by HPLC and evaluated on the contributions to overall taste. Aspartic acid and glutamic acid accounted for 8.77 to 147.98 mg/mL in ten commercial soy sauces samples. Lactic acid (ranging from 0.83 to 13.19 mg/mL) and pyroglutamic acid (ranging from 0 to 12.80 mg/mL) were the dominant organic acids, contributing to the acidity and ensuring a balance in taste of soy sauces. 5ʹ-Inosine monophosphate was the most abundant nucleotide, followed by 5ʹ-guanosine monophosphate, and they accounted for 0.30 to 3.54 mg/mL in ten soy sauces. According to the determination of non-volatile taste compounds in soy sauce samples, taste activity value (TAV) and equivalent umami concentration (EUC) of different soy sauces were calculated and compared. An exclusive cluster analysis based on TAV was proposed to classify the commercial soy sauces. The EUC value of new class A is much higher than other classes. ARTICLE HISTORY