Alcohol. 1991 Nov-Dec;8(6):467-71.
Anxiogenic behavior in rats during acute and protracted ethanol withdrawal: reversal by buspirone.

Lal H, Prather PL, Rezazadeh SM.

Department of Pharmacology, Texas College of Osteopathic Medicine, Ft. Worth 76107.

This study investigated the effectiveness of buspirone in reversing the anxiogenic behaviors occurring during ethanol withdrawal as measured in the elevated plus-maze. In response to anxiogenic drugs, rats spend less time in and make fewer entries onto the open arms of an elevated plus-maze, whereas anxiolytic drugs produce opposite effects. In this study, rats were fed a liquid diet containing 4.5% ethanol for 7 days. Twelve h (acute withdrawal) and 7 days (protracted withdrawal) following cessation of the ethanol diet, rats were tested on the elevated plus-maze. During these withdrawal periods, the percent open-arm entries and time spent on the open arms were significantly reduced relative to animals fed an ethanol-free diet, suggestive of anxiogenic-like symptoms. Buspirone (0.32-1.25 mg/kg) dose dependently reversed the withdrawal-induced decreases in open-arm activity. The anxiolytic-like activity of buspirone observed during ethanol withdrawal may be due to a reduction in serotonergic neurotransmission through activation of presynaptic 5-HT1A autoreceptors. The results obtained in this study suggest that pharmacotherapy with selective 5-HT1A agonists may be beneficial in alleviation of anxiety during ethanol withdrawal.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1781924&dopt=Abstract buspirone Buspar




Brain Res Bull. 1992 Apr;28(4):497-501.
Evidence for a postsynaptic action of the serotonergic anxiolytics: ipsapirone, indorenate and buspirone.

Fernandez-Guasti A, Lopez-Rubalcava C, Perez-Urizar J, Castaneda-Hernandez G.

Departamento de Farmacologia y Toxicologia, CINVESTAV, Mexico, D.F.

In the present experiment we analyzed whether the antianxiety action of the serotonergic 1A agonists buspirone (5 mg/kg), ipsapirone (5 mg/kg), indorenate (5 mg/kg), and 8-OH-DPAT (0.5 mg/kg) were mediated through the stimulation of pre- or postsynaptic serotonergic receptors. The experimental anxiety values were determined with the burying behavior test, where a reduction in the cumulative time of burying behavior was interpreted as a reduction in anxiety. To that purpose we analyzed the putative anxiolytic action of these drugs in animals with lesion of the serotonergic fibers after the intracerebroventricular (ICV) injection of 5,7-dihydroxytyptamine (5,7-DHT, 10 or 150 micrograms/10 microliters). The neurochemical analysis shows that these treatments produce a statistically significant reduction in 5-HT and 5-HIAA levels in various brain areas. The results of the behavioral experiments reveal that buspirone, ipsapirone, and indorenate produced exactly the same reduction in burying behavior in lesioned animals as compared with control rats. The reduction in burying behavior produced by 8-OH-DPAT was effectively prevented by the lesion with 5,7-DHT. These data suggest that the anxiolytic effect of buspirone, ipsapirone, and indorenate is mediated via the stimulation of postsynaptic receptors, while the somatodendritic receptors are involved in the antianxiety effect of 8-OH-DPAT.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1352175&dopt=Abstract buspirone Buspar




J Neural Transm Gen Sect. 1991;83(1-2):139-48.
5-HT1A agonists and dopamine: the effects of 8-OH-DPAT and buspirone on brain-stimulation reward.

Montgomery AM, Rose IC, Herberg LJ.

Institute of Neurology, National Hospital, London, United Kingdom.

Two specific 5-HT1A agonists, 8-OH-DPAT (0-300 micrograms/kg), and buspirone (0-3.0 mg/kg), were tested on variable-interval, threshold-current self-stimulation of rat lateral hypothalamus. Buspirone produced a prolonged monotonic depression of responding, whereas the effects of 8-OH-DPAT were biphasic: 3.0 micrograms/kg produced a sustained enhancement of responding while higher doses (100-300 micrograms/kg) produced a relatively short-lasting depression. This biphasic pattern parallels previously reported effects of 8-OH-DPAT on food intake and on various other behaviours. Threshold-current self-stimulation is highly sensitive to alterations in dopaminergic transmission but relatively insensitive to changes in 5-HT. Thus the facilitatory effect of low-dose 8-OH-DPAT seems most plausibly interpreted in terms of enhanced dopaminergic transmission. This could be brought about by 5HT1A autoreceptor-mediated inhibiton of 5-HT release and consequent disinhibition of dopaminergic transmission. Depression of self-stimulation by higher doses of 8-OH-DPAT may reflect the activity of 8-OH-DPAT at postsynaptic 5-HT receptors, with consequent inhibition of DA transmission. Suppression of responding after buspirone at all doses tested may reflect the action of this compound as a partial agonist at postsynaptic 5-HT receptors, and/or its effects on other systems.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1826841&dopt=Abstract buspirone Buspar




Life Sci. 1991;48(26):2505-11.
Antidepressant-like effects of buspirone mediated by the 5-HT1A post-synaptic receptors in the learned helplessness paradigm.

Martin P, Tissier MH, Adrien J, Puech AJ.

Departement de Pharmacologie, Faculte de Medecine Pitie-Salpetriere, Paris, France.

The 5-HT1A receptor agonists buspirone and 8-OH-DPAT have strong effects on serotoninergic systems. Mediated by both pre- and post-synaptic 5-HT1A receptors, these pharmacological effects might predict both antidepressant and antianxiety activities. In animal models sensitive to antidepressant drugs, the 5-HT1A agonists administered i.p. have been shown to mimic the behavioral effects of tricyclics. In the present study, the learned helplessness paradigm was used to assess the possible role of pre- or post-synaptic 5-HTIA receptors in this effect. The ability of buspirone compared with 8-OH-DPAT to reduce helpless behavior was investigated after local microinjections (0.1 or 1.0 micrograms in 0.5 microliters) into the raphe nuclei or into the septum. The results indicate that microinjections of buspirone or 8-OH-DPAT into the raphe nuclei did not reverse helpless behavior; in contrast, microinjections of both 5-HTIA agonists into the septum reverse helpless behavior. These results suggest that antidepressant-like properties of buspirone and 8-OH-DPAT may be mediated, in this test, by the post-synaptic 5-HTIA receptors through functional enhancement of the 5-HT transmission.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1828519&dopt=Abstract buspirone Buspar




Neuroscience. 1991;40(1):169-74.
Buspirone affects hippocampal rhythmical slow activity through serotonin1A rather than dopamine D2 receptors.

Coop CF, McNaughton N.

Department of Psychology, University of Otago, Dunedin, New Zealand.

Buspirone reduces anxiety clinically but, unlike classical anxiolytics, is not muscle relaxant, sedative, anticonvulsant or effective in increasing GABA function. The basis for its clinical action is not known, but action at both dopamine D2 and serotonin1A receptors has been suggested. Buspirone, like classical anxiolytics, produces a general reduction in the frequency of hippocampal rhythmical slow activity elicited by stimulation of the midbrain in the rat. Methysergide (3 mg/kg i.p.), GR38032F (0.3 mg/kg i.p.) and haloperidol (0.2 mg/kg and 2.0 mg/kg i.p.) failed to block this effect of buspirone (10 mg/kg i.p.). Apomorphine (0.3 mg/kg i.p.) had minor effects, but did not produce a general reduction in frequency. Pindolol (2 mg/kg i.p.) produced a small reduction in frequency itself. In the presence of pindolol, buspirone was without effect, while the effect of chlordiazepoxide (5 mg/kg i.p.) was potentiated. These results show that: (a) the similar effects of buspirone and classical anxiolytics such as chlordiazepoxide on reticular-elicited hippocampal rhythmical slow activity are achieved through different mechanisms; (b) the effects of buspirone in this particular test are more likely to depend on its interaction with serotonin1A receptors than its interaction with D2 receptors; and (c) that, as in other tests, buspirone does not act via serotonin2 or serotonin3 receptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1828866&dopt=Abstract buspirone Buspar




Psychopharmacology (Berl). 1991;104(1):132-6.
Effects of 5-HT-1A receptor agonists on CRF-induced behavior.

Lazosky AJ, Britton DR.

Department of Pharmacology and Molecular Biology, University of Health Sciences, Chicago Medical School, IL.

Buspirone (2.0 or 4.0 mg/kg) and 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT) (0.25 or 0.5 mg/kg) were used to examine the effects of serotonin 1A receptor agonists on the behavioral response of rats to centrally administered corticotropin-releasing factor (CRF). Behavioral observations were done with animals in their home cages. Parameters measured included locomotor activity, grooming and food consumption. CRF alone increased locomotor activity. 8-OH-DPAT also increased locomotion in both saline control and CRF-treated rats. Buspirone had no effect on basal locomotion or on CRF-induced hyperactivity. Both buspirone and 8-OH-DPAT antagonized CRF-induced grooming. Food consumption by fasted rats was suppressed by ICV CRF. 8-OH-DPAT suppressed eating by both ICV CRF and ICV saline-treated animals, while buspirone was without effect. These results demonstrate differences between the two putative 5-HT-1A agonists in their effects on CRF-induced behaviour but also demonstrate that both suppress CRF-induced grooming.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1831906&dopt=Abstract buspirone Buspar




Am J Psychiatry. 1991 Sep;148(9):1213-7.
Buspirone: sedative or stimulant effect?

Manfredi RL, Kales A, Vgontzas AN, Bixler EO, Isaac MA, Falcone CM.

Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey 17033.

OBJECTIVE: The primary objectives of this study were to evaluate the effects of initial and continued administration of buspirone on sleep induction and maintenance and sleep stage parameters, to determine the presence or absence of any drug-induced side effects, and to ascertain the presence or absence of sleep disturbances following abrupt withdrawal of the drug. METHOD: Six insomniac subjects who had chronic complaints of difficulty falling asleep and/or staying asleep and who were in good physical health, were not suffering from any major mental disorders, and had not used any medication for at least the last month participated in a 16-night sleep laboratory protocol. The protocol consisted of 4 placebo-baseline nights, 7 nights on which buspirone, 10 mg at bedtime, was administered, and 5 placebo-withdrawal nights. RESULTS: Wake time after sleep onset increased moderately during the first 3 nights of drug administration (there was a marked and significant increase on the first night) and increased by lesser degrees with continued drug administration. Overall, reports of side effects were infrequent. Following drug termination, there was a delayed and mild increase in sleep difficulty above baseline. CONCLUSIONS: These data not only confirm that buspirone lacks sedative effects but also suggest that the drug may have stimulant properties. Further, these findings suggest that buspirone has limited usefulness in anxious patients with concomitant sleep difficulties.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1883000&dopt=Abstract buspirone Buspar




J Pharmacol Exp Ther. 1992 Jul;262(1):90-8.
Profile of action of a novel 5-hydroxytryptamine1A receptor ligand E-4424 to inhibit aversive behavior in the mouse, rat and marmoset.

Costall B, Domeney AM, Farre AJ, Kelly ME, Martinez L, Naylor RJ.

Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire, England.

E-4424 (2-(4-[4-(4-chloro-1-pyrazolyl)butyl]-1-piperazinyl)pyrimidine) was shown to be a 5-hydroxytryptamine1A receptor ligand in radioligand binding assays and in an in vitro guinea pig ileum preparation had both 5-hydroxytryptamine1A antagonist and agonist effects. The antagonist/agonist ratio of E-4424 was greater than in the case of buspirone and ipsapirone. E-4424 was compared to diazepam, buspirone and ipsapirone to inhibit the behavioral response to an aversive situation in the mouse black and white test box, the rat social interaction test and a marmoset human threat test. The acute administration of E-4424 (0.0001-0.5 mg/kg, i.p.) to the mouse decreased aversion to the white area of the test box and was as effective as diazepam (0.125-1.0 mg/kg, i.p.) and much more potent than buspirone (0.25-1.0 mg/kg, i.p.) or ipsapirone (0.5-5.0 mg/kg, i.p.). E-4424 was also effective in enhancing rat social interaction and reducing anxiety-related behaviors in the marmoset and was again more potent than diazepam, buspirone or ipsapirone. Withdrawal from a 14-day administration of diazepam, cocaine, nicotine or alcohol exacerbated the response to the aversive situation in the mouse test. This was not observed after withdrawal from a chronic treatment with E-4424, buspirone or ipsapirone. However, E-4424 administered during drug withdrawal prevented the response caused by withdrawal from cocaine, alcohol, nicotine and diazepam: buspirone was ineffective and ipsapirone only attenuated that syndrome after alcohol withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1352556&dopt=Abstract buspirone Buspar