Serenic Explained

A serenic, or antiaggressive agent, is a type of drug which reduces the capacity for irritability and aggression.[1]

Examples

The recreational drug MDMA ("ecstasy") and a variety of related drugs have been described as empathogen-entactogens, or simply as entactogens.[2] These agents possess serenic and empathy-increasing properties in addition to their euphoriant effects, and have been associated with increased sociability, friendliness, and feelings of closeness to others as well as emotional empathy and prosocial behavior.[3] [4] The entactogenic effects of these drugs are thought to be related to their ability to temporarily increase the levels of certain brain chemicals, including serotonin,[5] dopamine, and, particularly, oxytocin.[6] [7]

Certain other serotonergic drugs, such as 5-HT1A receptor agonists, also increase oxytocin levels and may possess serenic properties as well.[8] The phenylpiperazine mixed 5-HT1A and 5-HT1B receptor agonists eltoprazine, fluprazine, and batoprazine have been described based on animal research as serenics.[9]

Agonists and antagonists of the receptors for the endogenous hormones oxytocin and vasopressin, respectively, have been shown to decrease aggressive behavior in scientific research, implicating them in the normal regulation of pathways involving aggressive behavior in the brain.[10] [11] Certain neurosteroids, such as allopregnanolone, also appear to play a role in the regulation of aggression, including, notably, sexually-dimorphic aggressive behavior.[12] The sex hormones testosterone and estradiol also regulate aggression.

Nicotinic acetylcholine receptors within the CNS, specifically α7 homopentameric receptors, are implicated in the regulation of aggression. The serenic effect of nicotine is well documented both in laboratory animals and humans, and, conversely, nicotinic receptor antagonists and nicotine withdrawal are associated with irritability and aggression.[13] [14] [15] Additionally, nicotinic receptors are required for rabies virus entry into a neuron, and the dysfunction of these neurons is implicated in the rabies-associated aggression.[16]

Notes and References

  1. Serenics and aggression . Olivier B, Mos J . 2 . 3 . 197–209 . 1532-2998 . 10.1002/smi.2460020305 . . Stress & Health . Chan DK . . 10 July 1986 .
  2. Bedi G, Hyman D, de Wit H . Is ecstasy an "empathogen"? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others . Biological Psychiatry . 68 . 12 . 1134–1140 . December 2010 . 20947066 . 2997873 . 10.1016/j.biopsych.2010.08.003 . Society of Biological Psychiatry . Brentwood, Tennessee, United States of America . 78009779 . Krystal JH . 424038458 .
  3. Hysek CM, Schmid Y, Simmler LD, Domes G, Heinrichs M, Eisenegger C, Preller KH, Quednow BB, Liechti ME . 6 . MDMA enhances emotional empathy and prosocial behavior . Social Cognitive and Affective Neuroscience . 9 . 11 . 1645–1652 . November 2014 . 24097374 . 4221206 . 10.1093/scan/nst161 . . Lieberman MD .
  4. Cami J, Farré M, Mas M, Roset PN, Poudevida S, Mas A, San L, de la Torre R . 6 . Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor performance and subjective effects . Journal of Clinical Psychopharmacology . 20 . 4 . 455–466 . August 2000 . 10917407 . 10.1097/00004714-200008000-00010 .
  5. Piper BJ, Fraiman JB, Owens CB, Ali SF, Meyer JS . Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram . Neuropsychopharmacology . 33 . 5 . 1192–1205 . April 2008 . 17609680 . 10.1038/sj.npp.1301491 . Brentwood, Tennessee, United States of America . Carlezon WA, George TP, Neumaier JF . . free .
  6. Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ, van Gerven JM, Buitelaar JK, Verkes RJ . 6 . Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration . Social Neuroscience . 4 . 4 . 359–366 . 2009 . 19562632 . 10.1080/17470910802649470 . 12310995 . Eslinger P, Boggio PS, Young L, Zahn R . 69984013 . London, United Kingdom of Great Britain . . 2006244001 .
  7. Broadbear JH, Kabel D, Tracy L, Mak P . Oxytocinergic regulation of endogenous as well as drug-induced mood . Pharmacology, Biochemistry, and Behavior . 119 . 1 . 61–71 . April 2014 . 23872370 . 10.1016/j.pbb.2013.07.002 . Koob JF, Schulteis G, Kantak KM, Arends M, Buisman-Pijlman FT, Broadbear JH, Zoltán S . 1787728 . Amsterdam, Netherlands . . 19772247 . 73644949 .
  8. de Boer SF, Koolhaas JM . 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis . European Journal of Pharmacology . 526 . 1–3 . 125–139 . December 2005 . 16310183 . 10.1016/j.ejphar.2005.09.065 . . Redegeld FA, Verri WA, Burk J . Amsterdam, Netherlands . sf97001017 . 01568459 .
  9. Olivier B . Serotonin and aggression . Annals of the New York Academy of Sciences . 1036 . 1 . 382–392 . December 2004 . 15817750 . 10.1196/annals.1330.022 . . New York City, New York, United States of America . 45595253 . 12037287 . 2004NYASA1036..382O . 01306678 .
  10. Calcagnoli F, de Boer SF, Althaus M, den Boer JA, Koolhaas JM . Antiaggressive activity of central oxytocin in male rats . Psychopharmacology . 229 . 4 . 639–651 . October 2013 . 23624810 . 10.1007/s00213-013-3124-7 . 481042 . de Witt H, Curran VH, Morrow AL, Hashimoto K, Howes O, Floresco SB, D'Souza D . Geneva, Switzerland . .
  11. Ferris CF, Lu SF, Messenger T, Guillon CD, Heindel N, Miller M, Koppel G, Robert Bruns F, Simon NG . 6 . Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior . Pharmacology, Biochemistry, and Behavior . 83 . 2 . 169–174 . February 2006 . 16504276 . 10.1016/j.pbb.2006.01.001 . Griebel G, Arends MA, Izenwasser S . Amsterdam, Netherlands . 24199104 . 67271683 .
  12. Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E . Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice . Neurochemical Research . 33 . 10 . 1990–2007 . October 2008 . 18473173 . 10.1007/s11064-008-9718-5 . . Geneva, Switzerland . Schousboe A . 19338424 .
  13. Lewis AS, Picciotto MR . Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies . Neuropharmacology . 167 . 107929 . May 2020 . 32058178 . 7080580 . 10.1016/j.neuropharm.2019.107929 .
  14. Lewis AS, Mineur YS, Smith PH, Cahuzac EL, Picciotto MR . Modulation of aggressive behavior in mice by nicotinic receptor subtypes . Biochemical Pharmacology . 97 . 4 . 488–497 . October 2015 . 26212554 . 4600457 . 10.1016/j.bcp.2015.07.019 . Nicotinic Acetylcholine Receptors as Therapeutic Targets: Emerging Frontiers in Basic Research and Clinical Science (Satellite to the 2015 Meeting of the Society for Neuroscience) Oct 14-15, Chicago, IL USA .
  15. Picciotto MR, Lewis AS, van Schalkwyk GI, Mineur YS . Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states . Neuropharmacology . 96 . Pt B . 235–243 . September 2015 . 25582289 . 4486625 . 10.1016/j.neuropharm.2014.12.028 . The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition .
  16. Hueffer K, Khatri S, Rideout S, Harris MB, Papke RL, Stokes C, Schulte MK . Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS . Scientific Reports . 7 . 1 . 12818 . October 2017 . 28993633 . 5634495 . 10.1038/s41598-017-12726-4 . 2017NatSR...712818H .

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