A Five Minute Experience in the Elevated Plus-maze Alters the State of the Benzodiazepine Receptor in the Dorsal Raphe Nucleus

Overview

Journal J Neurosci

Specialty Neurology

Date 1997 Feb 15

PMID 9006991

Citations 21

Authors

L E Gonzalez

S E File

Affiliations

Soon will be listed here.

Abstract

A single 5 min exposure to the elevated plus-maze test of anxiety renders animals insensitive to the anxiolytic effects of the benzodiazepines in this test. The purpose of the present experiments was to explore whether this phenomenon resulted from a change in the functional state of benzodiazepine receptors in the dorsal raphe nucleus. The benzodiazepine receptor agonist midazolam (0.5, 1, and 2 microg) and antagonist flumazenil (100 and 500 ng) were directly administered to the dorsal raphe nucleus in rats either naive to, or with one previous 5 min exposure of, the elevated plus-maze. In naive rats, midazolam produced significant anxiolytic effects at all doses, and flumazenil was silent. In plus-maze-experienced rats, midazolam no longer had anxiolytic effects in the plus-maze, but flumazenil did, indicating that the previous experience of the maze had changed the state of the benzodiazepine receptor. This changed receptor function generalized to the social interaction test. Thus, in naive animals tested in high light, midazolam (0.5, 1, and 2 microg) had significant anxiolytic effects and flumazenil (100 and 500 ng) was silent, whereas in plus-maze-experienced rats both midazolam (1 microg) and flumazenil (500 ng) had significant anxiolytic effects. Extensive analysis of locomotor activity in both tests showed that the changed responsivity to midazolam could not be explained by habituation, because on none of the measures used was there any difference in motor activity scores between plus-maze-naive and experienced rats.

Citing Articles

A mild stressor induces short-term anxiety and long-term phenotypic changes in trauma-related behavior in female rats.

Shanazz K, Nalloor R, Vazdarjanova A Front Behav Neurosci. 2023; 17:1231563.

PMID: 37732174 PMC: 10507355. DOI: 10.3389/fnbeh.2023.1231563.

Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling.

Vasavda C, Semenza E, Liew J, Kothari R, Dhindsa R, Shanmukha S Sci Signal. 2022; 15(733):eabh3066.

PMID: 35536885 PMC: 9281001. DOI: 10.1126/scisignal.abh3066.

Sex differences in specific aspects of two animal tests of anxiety-like behavior.

Sergio T, Wetherill L, Kwok C, Khoyloo F, Hopf F Psychopharmacology (Berl). 2021; 238(10):2775-2787.

PMID: 34120205 PMC: 11071636. DOI: 10.1007/s00213-021-05893-w.

Effects of test experience, closed-arm wall color, and illumination level on behavior and plasma corticosterone response in an elevated plus maze in male C57BL/6J mice: a challenge against conventional interpretation of the test.

Shoji H, Miyakawa T Mol Brain. 2021; 14(1):34.

PMID: 33588907 PMC: 7885464. DOI: 10.1186/s13041-020-00721-2.

Wireless, battery-free subdermally implantable photometry systems for chronic recording of neural dynamics.

Burton A, Obaid S, Vazquez-Guardado A, Schmit M, Stuart T, Cai L Proc Natl Acad Sci U S A. 2020; 117(6):2835-2845.

PMID: 31974306 PMC: 7022161. DOI: 10.1073/pnas.1920073117.

References

Lee E, Wang F, Tang Y, Geyer M . Gabaergic interneurons in the dorsal raphe mediate the effects of apomorphine on serotonergic system. Brain Res Bull. 1987; 18(3):345-53. DOI: 10.1016/0361-9230(87)90012-8. View

File S . One-trial tolerance to the anxiolytic effects of chlordiazepoxide in the plus-maze. Psychopharmacology (Berl). 1990; 100(2):281-2. DOI: 10.1007/BF02244419. View

Thiebot M, Jobert A, Soubrie P . Conditioned suppression of behavior: its reversal by intra raphe microinjection of chlordiazepoxide and GABA. Neurosci Lett. 1980; 16(2):213-7. DOI: 10.1016/0304-3940(80)90347-x. View

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

Baraban J, Aghajanian G . Noradrenergic innervation of serotonergic neurons in the dorsal raphe: demonstration by electron microscopic autoradiography. Brain Res. 1981; 204(1):1-11. DOI: 10.1016/0006-8993(81)90646-6. View

Thiebot M, Jobert A, Soubrie P . Chlordiazepoxide and GABA injected into raphé dorsalis release the conditioned behavioural suppression induced in rats by a conflict procedure without nociceptive component. Neuropharmacology. 1980; 19(7):633-41. DOI: 10.1016/0028-3908(80)90037-4. View

Pellow S, Chopin P, File S, Briley M . Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985; 14(3):149-67. DOI: 10.1016/0165-0270(85)90031-7. View

Sprouse J, Aghajanian G . Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse. 1987; 1(1):3-9. DOI: 10.1002/syn.890010103. View

Laurent J, Mangold M, Humbel U, Haefely W . Reduction by two benzodiazepines and pentobarbitone of the multiunit activity in substantia nigra, hippocampus, nucleus locus coeruleus and nucleus raphé dorsalis of encéphale isolé rats. Neuropharmacology. 1983; 22(4):501-11. DOI: 10.1016/0028-3908(83)90170-3. View

10.

Treit D, Menard J, Royan C . Anxiogenic stimuli in the elevated plus-maze. Pharmacol Biochem Behav. 1993; 44(2):463-9. DOI: 10.1016/0091-3057(93)90492-c. View

11.

File S, Gonzalez L . Anxiolytic effects in the plus-maze of 5-HT1A-receptor ligands in dorsal raphé and ventral hippocampus. Pharmacol Biochem Behav. 1996; 54(1):123-8. DOI: 10.1016/0091-3057(95)02108-6. View

12.

Maier S, Busch C, Maswood S, Grahn R, Watkins L . The dorsal raphe nucleus is a site of action mediating the behavioral effects of the benzodiazepine receptor inverse agonist DMCM. Behav Neurosci. 1995; 109(4):759-66. DOI: 10.1037//0735-7044.109.4.759. View

13.

File S . The interplay of learning and anxiety in the elevated plus-maze. Behav Brain Res. 1993; 58(1-2):199-202. DOI: 10.1016/0166-4328(93)90103-w. View

14.

Wang Q, Nakai Y . Enkephalinergic innervation of GABAergic neurons in the dorsal raphe nucleus of the rat. Brain Res Bull. 1993; 32(3):315-20. DOI: 10.1016/0361-9230(93)90193-f. View

15.

Lister R . The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berl). 1987; 92(2):180-5. DOI: 10.1007/BF00177912. View

16.

Rodgers R, Shepherd J . Influence of prior maze experience on behaviour and response to diazepam in the elevated plus-maze and light/dark tests of anxiety in mice. Psychopharmacology (Berl). 1993; 113(2):237-42. DOI: 10.1007/BF02245704. View

17.

Graeff F, Viana M, Mora P . Opposed regulation by dorsal raphe nucleus 5-HT pathways of two types of fear in the elevated T-maze. Pharmacol Biochem Behav. 1996; 53(1):171-7. DOI: 10.1016/0091-3057(95)02012-8. View

18.

Gonzalez L, Andrews N, File S . 5-HT1A and benzodiazepine receptors in the basolateral amygdala modulate anxiety in the social interaction test, but not in the elevated plus-maze. Brain Res. 1996; 732(1-2):145-53. DOI: 10.1016/0006-8993(96)00517-3. View

19.

Thiebot M, Soubrie P, Hamon M, Simon P . Evidence against the involvement of serotonergic neurons in the anti-punishment activity of diazepam in the rat. Psychopharmacology (Berl). 1984; 82(4):355-9. DOI: 10.1007/BF00427685. View

20.

Higgins G, Jones B, Oakley N . Effect of 5-HT1A receptor agonists in two models of anxiety after dorsal raphe injection. Psychopharmacology (Berl). 1992; 106(2):261-7. DOI: 10.1007/BF02801982. View