Differential role of CREB in novelty‐seeking behavior by adolescent and adult rats

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.

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Development of sensitivity to cAMP-inducing hormones in the rat stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.247.3.g231 ◽

1984 ◽

Vol 247 (3) ◽

pp. G231-G239

Author(s):

C. Gespach ◽

Y. Cherel ◽

G. Rosselin

Keyword(s):

Biological Activities ◽

Physiological Role ◽

H2 Receptor Antagonist ◽

Adult Rats ◽

Gastric Glands ◽

Camp Generation ◽

Final Maturation ◽

Noncompetitive Inhibitor ◽

Regulatory Properties

Development of cAMP responses to secretin, pancreatic glucagon, and histamine was measured in gastric glands of fetal (day 20), postnatal (days 1-30), and adult rats (day 65). cAMP stimulation by these hormones was already detected on day 20 of gestation. cAMP generation showed biphasic variations during the 1st days of life and at the onset of weaning (day 20). Anticipated weaning at day 14 triggered precocious maturation (efficacies) of the cAMP-generating systems sensitive to secretin, glucagon, and histamine without changing the potencies of the hormones. During development, the general characteristics (potency and pharmacological or regulatory properties) of the receptor-cAMP systems studied were comparable with those evidenced in adult rats. At days 5, 20, and 65, vasoactive intestinal peptide and the peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) were about 100 times less potent than secretin (EC50 = 1.5 X 10(-9) M secretin). The histamine action could be blocked by the competitive H2-receptor antagonist cimetidine (70-100% inhibition) as well as by the noncompetitive inhibitor somatostatin (37-62% inhibition). The data indicate that these regulatory hormones (secretin, glucagon(s), histamine, and somatostatin) might have a direct effect on gastric glands and may modulate their biological activities (metabolism, differentiation, proliferation, and exocrine and endocrine secretions) from the neonatal period in rats. The important physiological role of weaning on the final maturation of the cAMP-generating systems in rat gastric glands is underlined.

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Sex- and age-based differences in the effect of central serotonin on arterial blood pressure regulation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00414.2020 ◽

2020 ◽

Vol 129 (6) ◽

pp. 1310-1323

Author(s):

Jennifer L. Magnusson ◽

Craig A. Emter ◽

Kevin J. Cummings

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Nrem Sleep ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

Adult Rats ◽

Arterial Blood ◽

Serotonin Neurons ◽

Older Males

The role of serotonin in arterial blood pressure (ABP) regulation across states of vigilance is unknown. We hypothesized that adult rats devoid of CNS serotonin (TPH2−/−) have low ABP in wakefulness and NREM sleep, when serotonin neurons are active. However, TPH2−/− rats experience higher ABP than TPH2+/+ rats in wakefulness and REM only, a phenotype present only in older males and not females. CNS serotonin may be critical for preventing high ABP in males with aging.

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