Evidence Against the Involvement of Serotonergic Neurons in the Anti-punishment Activity of Diazepam in the Rat

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1984 Jan 1

PMID 6427828

Citations 14

Authors

M H Thiebot

P Soubrie

M Hamon

P Simon

Affiliations

Soon will be listed here.

Abstract

The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 microgram in 0.4 microliter) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 micrograms in 0.5 microliter) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10(-5)-10(-4)M in 0.2 microliter) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.

Citing Articles

Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT1A Receptor.

Mi G, Liu S, Zhang J, Liang H, Gao Y, Li N PLoS One. 2017; 12(1):e0168964.

PMID: 28085967 PMC: 5234788. DOI: 10.1371/journal.pone.0168964.

Evaluation of anxiolytic potency of essential oil and S-(+)-linalool from Cinnamomum osmophloeum ct. linalool leaves in mice.

Cheng B, Sheen L, Chang S J Tradit Complement Med. 2015; 5(1):27-34.

PMID: 26151006 PMC: 4488179. DOI: 10.1016/j.jtcme.2014.10.007.

The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders.

Olivier J, Vinkers C, Olivier B Front Pharmacol. 2013; 4:74.

PMID: 23781201 PMC: 3677985. DOI: 10.3389/fphar.2013.00074.

5-HT1A receptor blockade reverses GABA(A) receptor alpha3 subunit-mediated anxiolytic effects on stress-induced hyperthermia.

Vinkers C, van Oorschot R, Korte S, Olivier B, Groenink L Psychopharmacology (Berl). 2010; 211(2):123-30.

PMID: 20535452 PMC: 2892061. DOI: 10.1007/s00213-010-1895-7.

A five minute experience in the elevated plus-maze alters the state of the benzodiazepine receptor in the dorsal raphe nucleus.

Gonzalez L, File S J Neurosci. 1997; 17(4):1505-11.

PMID: 9006991 PMC: 6793746.

References

Gallager D . Benzodiazepines: potentiation of a GABA inhibitory response in the dorsal raphe nucleus. Eur J Pharmacol. 1978; 49(2):133-43. DOI: 10.1016/0014-2999(78)90069-9. View

Graeff F, Schoenfeld R . Tryptaminergic mechanisms in punished and nonpunished behavior. J Pharmacol Exp Ther. 1970; 173(2):277-83. View

MARGULES D, Stein L . Increase of "antianxiety" activity and tolerance of behavioral depression during chronic administration of oxazepam. Psychopharmacologia. 1968; 13(1):74-80. DOI: 10.1007/BF00401620. View

Thiebot M, Hamon M, Soubrie P . The involvement of nigral serotonin innervation in the control of punishment-induced behavioral inhibition in rats. Pharmacol Biochem Behav. 1983; 19(2):225-9. DOI: 10.1016/0091-3057(83)90043-6. View

Giambalvo C, Snodgrass S . Biochemical and behavioral effects of serotonin neurotoxins on the nigrostriatal dopamine system: comparison of injection sites. Brain Res. 1978; 152(3):555-66. DOI: 10.1016/0006-8993(78)91110-1. View

Petersen E, LASSEN J . A water lick conflict paradigm using drug experienced rats. Psychopharmacology (Berl). 1981; 75(3):236-9. DOI: 10.1007/BF00432430. View

Hamon M, Bourgoin S, Hery F, Simmonet G . Phospholipid-induced activation of tryptophan hydroxylase from the rat brainstem. Biochem Pharmacol. 1978; 27(6):915-22. DOI: 10.1016/0006-2952(78)90419-7. View

ROBICHAUD R, Sledge K . The effects of p-chlorophenylalanine on experimentally induced conflict in the rat. Life Sci. 1969; 8(17):965-9. DOI: 10.1016/0024-3205(69)90427-5. View

Simon P, Soubrie P . Behavioral studies to differentiate anxiolytic and sedative activity of the tranquilizing drugs. Mod Probl Pharmacopsychiatry. 1979; 14:99-143. View

10.

Wilbur R, Kulik F . Gray's cybernetic theory of anxiety. Lancet. 1981; 2(8250):803. DOI: 10.1016/s0140-6736(81)90204-x. View

11.

Soubrie P, Blas C, Ferron A, Glowinski J . Chlordiazepoxide reduces in vivo serotonin release in the basal ganglia of encéphale isolé but not anesthetized cats: evidence for a dorsal raphe site of action. J Pharmacol Exp Ther. 1983; 226(2):526-32. View

12.

Shephard R, BROADHURST P . Effects of diazepam and of serotonin agonists on hyponeophagia in rats. Neuropharmacology. 1982; 21(4):337-40. DOI: 10.1016/0028-3908(82)90097-1. View

13.

Stein L, WISE C, Belluzzi J . Effects of benzodiazepines on central serotonergic mechanisms. Adv Biochem Psychopharmacol. 1975; (14):29-44. View

14.

Trulson M, Preussler D, Howell G, Frederickson C . Raphe unit activity in freely moving cats: effects of benzodiazepines. Neuropharmacology. 1982; 21(10):1045-50. DOI: 10.1016/0028-3908(82)90120-4. View

15.

GELLER I, Blum K . The effects of 5-HTP on para-Chlorophenylalanine (p-CPA) attenuation of "conflict" behavior. Eur J Pharmacol. 1970; 9(3):319-24. DOI: 10.1016/0014-2999(70)90229-3. View

16.

Shephard R, Buxton D, BROADHURST P . Drug interactions do not support reduction in serotonin turnover as the mechanism of action of benzodiazepines. Neuropharmacology. 1982; 21(10):1027-32. DOI: 10.1016/0028-3908(82)90117-4. View

17.

Rydin E, SCHALLING D, Asberg M . Rorschach ratings in depressed and suicidal patients with low levels of 5-hydroxyindoleacetic acid in cerebrospinal fluid. Psychiatry Res. 1982; 7(2):229-43. DOI: 10.1016/0165-1781(92)90096-l. View

18.

CORRODI H, Fuxe K, Lidbrink P, Olson L . Minor tranquillizers, stress and central catecholamine neurons. Brain Res. 1971; 29(1):1-16. DOI: 10.1016/0006-8993(71)90413-6. View

19.

Bonetti E, Pieri L, Cumin R, SCHAFFNER R, Pieri M, Gamzu E . Benzodiazepine antagonist Ro 15-1788: neurological and behavioral effects. Psychopharmacology (Berl). 1982; 78(1):8-18. DOI: 10.1007/BF00470579. View

20.

Davis N, Gray J . Brain 5-hydroxytryptamine and learned resistance to punishment. Behav Brain Res. 1983; 8(2):129-37. DOI: 10.1016/0166-4328(83)90049-9. View