J Mammary Gland Biol Neoplasia. 2014 Mar;19(1):139-46. doi: 10.1007/s10911-013-9304-6. Epub 2013 Oct 18. Serotonin and serotonin transport in the regulation of lactation. Marshall AM1, Hernandez LL, Horseman ND. Author information

Abstract Serotonin (5-HT), classically known as a neurotransmitter involved in regulating sleep, appetite, memory, sexual behavior, neuroendocrine function and mood is also synthesized in epithelial cells located in many organs throughout the body, including the mammary gland. The function of epithelial 5-HT is dependent on the expression of the 5-HT receptors in a particular system. The conventional components of a classic 5-HT system are found within the mammary gland; synthetic enzymes (tryptophan hydroxylase I, aromatic amino acid decarboxylase), several 5-HT receptors and the 5-HT reuptake transporter (SERT). In the mammary gland, two actions of 5-HT through two different 5-HT receptor subtypes have been described: negative feedback on milk synthesis and secretion, and stimulation of parathyroid hormone related-protein, a calcium-mobilizing hormone. As with neuronal systems, the regulation of 5-HT activity is multifactorial, but one seminal component is reuptake of 5-HT from the extracellular space following its release. Importantly, the wide availability of selective 5-HT reuptake inhibitors (SSRI) allows the manipulation of 5-HT activity in a biological system. Here, we review the role of 5-HT in mammary gland function, review the biochemistry, genetics and physiology of SERT, and discuss how SERT is vital to the function of the mammary gland.

http://www.ncbi.nlm.nih.gov/pubmed?term=Marshall%20AM%5BAuthor%5D&cauthor=true&cauthor_uid=24136337http://www.ncbi.nlm.nih.gov/pubmed?term=Hernandez%20LL%5BAuthor%5D&cauthor=true&cauthor_uid=24136337http://www.ncbi.nlm.nih.gov/pubmed?term=Horseman%20ND%5BAuthor%5D&cauthor=true&cauthor_uid=24136337

Drug Test Anal. 2014 Jan-Feb;6(1-2):7-16. doi: 10.1002/dta.1574. Epub 2013 Nov 11. Analytical approaches for the determination of phytocannabinoids and endocannabinoids in human matrices. Battista N1, Sergi M, Montesano C, Napoletano S, Compagnone D, Maccarrone M. Author information

Abstract Over the last two decades, the role played by phytocannabinoids and endocannabinoids in medicine has gained increasing interest in the scientific community. Upon identification of the plant compound (9)-tetrahydrocannabinol (THC) and of the endogenous substance anandamide (AEA), different methodological approaches and innovative techniques have been developed, in order to evaluate the content of these molecules in various human matrices. In this review, we discuss the analytical methods that are currently used for the identification of phytocannabinoids and endocannabinoids, and we summarize the benefits and limitations of these procedures. Moreover, we provide an overview of the main biological matrices that have been analyzed to date for qualitative detection and quantitative determination of these compounds.

http://www.ncbi.nlm.nih.gov/pubmed?term=Battista%20N%5BAuthor%5D&cauthor=true&cauthor_uid=24218186http://www.ncbi.nlm.nih.gov/pubmed?term=Sergi%20M%5BAuthor%5D&cauthor=true&cauthor_uid=24218186http://www.ncbi.nlm.nih.gov/pubmed?term=Montesano%20C%5BAuthor%5D&cauthor=true&cauthor_uid=24218186http://www.ncbi.nlm.nih.gov/pubmed?term=Napoletano%20S%5BAuthor%5D&cauthor=true&cauthor_uid=24218186http://www.ncbi.nlm.nih.gov/pubmed?term=Compagnone%20D%5BAuthor%5D&cauthor=true&cauthor_uid=24218186http://www.ncbi.nlm.nih.gov/pubmed?term=Maccarrone%20M%5BAuthor%5D&cauthor=true&cauthor_uid=24218186

Peptides. 2003 May;24(5):779-88. Emotion regulation and touch in infants: the role of cholecystokinin and opioids. Weller A1, Feldman R. Author information

Abstract Behavioral-pharmacological research in infant rats supports the role of cholecystokinin (CCK) and opioid peptides in mediating early learning of new associations with aspects of the nest and dam, such as maternal odor, milk, and contact. The current paper reviews research that examines the hypothesis that these neuropeptide systems are further involved in mediating emotion regulation in infants, thus playing a role in the emergence of stress-reactivity and other motivational systems. The beneficial effects of maternal proximity, handling, and touch on the development of emotion regulation have been demonstrated in both human and animal models. Interventions that promote tactile stimulation of the infant ("touch therapy") and infant-mother contact ("skin-to-skin contact" or "kangaroo care") have been shown to improve the infant's ability to self-regulate, and to moderate the effects of some risk factors. Theoretical perspectives and empirical findings regarding emotion regulation in infants are first discussed. This is followed by a review of work providing evidence in animal models (and suggestive evidence in humans) for the importance of CCK and opioid neuropeptides in affecting infant emotion regulation and the impact of touch-based interventions, in particular in the context of infant-mother attraction, contact, separation, and attachment. PMID: 12895666 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed?term=Weller%20A%5BAuthor%5D&cauthor=true&cauthor_uid=12895666http://www.ncbi.nlm.nih.gov/pubmed?term=Feldman%20R%5BAuthor%5D&cauthor=true&cauthor_uid=12895666

Molculas basadas en la felicidad.

Primera serie de molculas Indice observado % Normales (%)De felicidad 98 95 - 100

de risa 99 95 - 100de alegra 95 95 - 100de jbilo 96 95 - 100

de exaltacin 99 95 - 100de gozo 95 95 - 100

de satisfaccin 97 95 - 100de encanto 99 95 - 100de contento 98 95 - 100

de optimismo 96 95 - 100de placer 99 95 - 100

de bienestar 98 95 - 100de goce 96 95 - 100

de euforia 97 95 - 100de xtasis 99 95 - 100

Molculas basadas en la tristezaPrimera serie de molculas Indice observado % Normales (%)

De pesar 0 0 - 5de sufrimieto 0 0 - 5de tristeza 0 0 - 5de pena 0 0 - 5

de desolacin 0 0 - 5de desgarro 0 0 - 5de afliccin 0 0 - 5de tormento 0 0 - 5de marasmo 0 0 - 5

de melancola 0 0 - 5de abatimiento 0 0 - 5

de angustia 0 0 - 5de dolor moral 0 0 - 5de depresin 0 0 - 5de desgano 0 0 - 5

de pesimismo 0 0 - 5

Molculas basadas en la tristezaPrimera serie de molculas Indice observado % Normales (%)

De pesar 60 0 - 5de sufrimiento 40 0 - 5

de tristeza 30 0 - 5de pena 90 0 - 5

de desolacin 40 0 - 5de desgarro 20 0 - 5de afliccin 70 0 - 5de tormento 20 0 - 5de marasmo 20 0 - 5

de melancola 50 0 - 5de abatimiento 20 0 - 5

de angustia 40 0 - 5de dolor moral 30 0 - 5de depresin 20 0 - 5de desgano 20 0 - 5

de pesimismo 10 0 - 5

Molculas basadas en la felicidad.

Primera serie de molculas Indice observado % Normales (%)De felicidad 30 95 - 100

de risa 30 95 - 100de alegra 30 95 - 100de jbilo 20 95 - 100

de exaltacin 40 95 - 100de gozo 40 95 - 100

de satisfaccin 30 95 - 100de encanto 70 95 - 100de contento 40 95 - 100

de optimismo 70 95 - 100de placer 50 95 - 100

de bienestar 30 95 - 100de goce 60 95 - 100

de euforia 40 95 - 100de xtasis 50 95 - 100

Hormones and neurotransmitters in milkE. Hazum Department of Hormone Research, The Weizmann Institute of Science, Rehovot, 76100, Israel

Abstract Several hormones and neurotransmitters are present in milk from humans and other mammals, e.g. gonadotropin-releasing hormone, thyrotropin-releasing hormone, epidermal growth factor, morphiceptin and -casomorphin, morphine, TSH, ACTH, prolactin, gonadotropins, etc. The presence of significant quantities of these hormones and neurotransmitters in milk raises the question not only of their role but also of their origin. They can be synthesized or processed in the mammary gland or excreted into milk through various pathways. In the suckling mammals, the hormones and neurotransmitters may gain entrance into the body through the gastrointestinal tract and could have physiological and pharmacological significance by interacting with their specific receptors.

Endocannabinoids and Food Intake: Newborn Suckling and Appetite Regulation in Adulthood

SUMMARY. Cannabinoids are known to enhance appetite by activating cannabinoid (CB1) receptors. This phenomenon is exploited to combat cachexia and loss of appetite in cancer and AIDS patients. The endocannabinoid 2-arachidonylglycerol (2-AG) is present in milk. Evi- dence is presented supporting a critical role for CB1 receptors in survival of mouse pups. Thus neonates do not gain weight and die within the first week of life when their receptors are blocked. This is due apparently, to an inabil- ity to ingest maternal milk. This suggests that the endocannabinoid-CB1 re- ceptor system is unique in its absolute control over the initiation of the neonatal milk suckling response. It is further

proposed that cannabis-based medicines should be developed to benefit infant failure to thrive.

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Exp Biol Med (Maywood). 2005 Apr;230(4):225-34. Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood. Fride E1, Bregman T, Kirkham TC.

Abstract The appetite-stimulating effects of the cannabis plant (Cannabis sativa) have been known since ancient times, and appear to be effected through the incentive and rewarding properties of foods. Investigations into the biological basis of the multiple effects of cannabis have yielded important breakthroughs in recent years: the discovery of two cannabinoid receptors in brain and peripheral organ systems, and endogenous ligands (endocannabinoids) for these receptors. These advances have greatly increased our understanding of how appetite is regulated through these endocannabinoid receptor systems. The presence of endocannabinoids in the developing brain and in maternal milk have led to evidence for a critical role for CB1 receptors in oral motor control of suckling during neonatal development. The endocannabinoids appear to regulate energy balance and food intake at four functional levels within the brain and periphery: (i) limbic system (for hedonic evaluation of foods), (ii) hypothalamus and hindbrain (integrative functions), (iii) intestinal system, and (iv) adipose tissue. At each of these levels, the endocannabinoid system interacts with a number of better known molecules involved in appetite and weight regulation, including leptin, ghrelin, and the melanocortins. Therapeutically, appetite stimulation by cannabinoids has been studied for several decades, particularly in relation to cachexia and malnutrition associated with cancer, acquired immunodeficiency syndrome, or anorexia nervosa. The recent advances in cannabinoid pharmacology may lead to improved treatments for these conditions or, conversely, for combating excessive appetite and body weight, such as CB1 receptor antagonists as antiobesity medications. In conclusion, the exciting progress in the understanding of how the endocannabinoid CB receptor systems influence appetite and body weight is stimulating the development of therapeutic orexigenic and anorectic agents. Furthermore, the role of cannabinoid CB1 receptor activation for milk suckling in newborns may open new doors toward understanding nonorganic failure-to-thrive in infants, who display growth failure without known organic cause.

http://www.ncbi.nlm.nih.gov/pubmed?term=Fride%20E%5BAuthor%5D&cauthor=true&cauthor_uid=15792943http://www.ncbi.nlm.nih.gov/pubmed?term=Bregman%20T%5BAuthor%5D&cauthor=true&cauthor_uid=15792943http://www.ncbi.nlm.nih.gov/pubmed?term=Kirkham%20TC%5BAuthor%5D&cauthor=true&cauthor_uid=15792943