Pharmacol Biochem Behav. 1998 Oct;61(2):207-14.
Avoidance of time-out from response-independent food presentation: effects of chlordiazepoxide and buspirone.

van Haaren F, Anderson KG.

University of Florida, Gainesville 32611-2250, USA.

Five male Wistar rats were exposed to a two- component multiple schedule. In one component, signaled by a tone, food pellets were presented on a random-time 120-s schedule. In the other component, food pellets were presented on a random-time 30-s schedule. Pellets were only presented during a 10-s time-in period that alternated with a 50-s time-out period, unless the subject pressed a lever to postpone time-out presentation by 20 s. Response-independent food pellets were never presented within 2 s of this avoidance response. For most subjects avoidance rates were consistently higher when response-independent food pellets were delivered infrequently than when they were delivered more often. The amount of time spent in time-in varied considerably between subjects but was not consistently related to the frequency of response-independent pellet presentation. Once stable response rates were established subjects were intraperitoneally injected with different doses of chlordiazepoxide (1, 3, 10, 17, or 30 mg/kg) or buspirone (0.1, 0.3, 1.0, 1.7, 3.0, or 4.2 mg/kg). Low doses of chlordiazepoxide either did not affect or slightly increased avoidance response rates, whereas higher doses (10 mg/kg and up) produced a dose-dependent decrease in avoidance responding. The time subjects spent in the presence of stimuli associated with the availability of response-independent food either did not change or increased slightly after the lower doses of chlordiazepoxide, while it decreased dose dependently following the higher doses. Low doses of buspirone increased avoidance rates in subjects first exposed to chlordiazepoxide, but did not alter rates in the remaining subjects. Intermediate doses of buspirone decreased avoidance rates more in the component with the lower frequency of pel




Pol J Pharmacol. 1998 Mar-Apr;50(2):117-24.
Antidepressant-like properties of some serotonin receptor ligands and calcium channel antagonists measured with the forced swimming test in mice.

Biala G.

Department of Pharmacodynamics, Medical Academy, Lublin, Poland.

This study has examined the effects of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), buspirone, nifedipine and verapamil on duration of immobility in the forced swimming test in mice. The 5-HT1A agonist-8-OH-DPAT (0.25, 0.5, 1 mg/kg) and dihydropyridine calcium channel antagonist-nifedipine (10 mg/kg) produced decreases in immobility time. These effects were similar to those of the tricyclic antidepressant-imipramine (5 and 10 mg/kg). Non-dihydropyridine calcium channel antagonist-verapamil (10 and 20 mg/kg) had no effect on immobility time. The non-benzodiazepine anxiolytic and 5-HT1A agonist-buspirone (1 mg/kg) when given in a single injection or as repeated treatment, did not exert antidepressant-like activity in the forced swimming test. Pretreatment with dopamine antagonist-haloperidol (0.5 mg/kg) significantly antagonized the effects of 8-OH-DPAT (1 mg/kg), imipramine (10 mg/kg) and nifedipine (10 mg/kg). Pretreatment with benzodiazepine anxiolytic-diazepam (2 mg/kg) antagonized the effect of imipramine (10 mg/kg) but not that of 8-OH-DPAT (1 mg/kg) or nifedipine (10 mg/kg). Neither haloperidol nor diazepam produced any effects in this test. Single or repeated administration of buspirone (1 mg/kg) did not alter the reduction of immobility time produced by imipramine (10 mg/kg). These results suggest that 5-HT1A agonists and dihydropyridine calcium channel blockers may have antidepressant efficacy in the forced swimming test, but the effects of buspirone and 8-OH-DPAT may be mediated via different mechanisms. These results also indicate that the relationship between serotonin and dopamine neurons may play a role in the action of antidepressant drugs. In addition, the interactions involving both GABAergic and serotoninergic




Pharmacol Biochem Behav. 1998 Dec;61(4):451-7.
Level of punishment determines anticonflict activity of ondansetron in pigeons: comparison with buspirone and diazepam.

Castejon AM, Cubeddu LX.

Department of Pharmacology, School of Pharmacy, Central University of Venezuela, Caracas.

The anticonflict effect of the selective 5-HT3 receptor antagonist, ondansetron, was investigated employing an operant conflict task in pigeons. Behavior (key pecking) was stimulated by food presentation. A fixed-interval program of alternated punished (electrical shocks) and unpunished responding was employed. The effects of drugs were evaluated at two levels punishment intensity; i.e., baseline responding during the punished interval was 5% (higher punishment) or 10% (lower punishment) of the unpunished responding rate. Ondansetron released responding suppressed by punishment only when pigeons were working at the lower levels of punishment. Under these conditions, ondansetron (100 microg/kg, i.v.), increased key pecking by 119% above control and vehicle values, and doubled the number of shocks received by the pigeons during the punished intervals. Similarly to ondansetron, the anticonflict effects of buspirone (0.3 and 1 mg/kg) and diazepam (1 and 1.5 mg/kg) were strongly dependent on the intensity of the punishing stimulus. When punished responding was suppressed to 5% of unpunished responding by applying shocks of higher intensity, diazepam and buspirone had negligible anticonflict action. However, at lower levels of punishment, diazepam and buspirone produced much greater anticonflict effects than ondansetron (p < 0.001). These results indicate that ondansetron exhibits a modest effect in releasing behaviors suppressed by punishment (anxiolytic-like action), which was highly dependent on the intensity of punishment applied. It is proposed that the anxiogenic response to punishment is less sensitive to 5-HT3 antagonists than the behavior induced by aversive, unpunished situations, where 5-HT3 antagonists have show




Behav Brain Res. 1998 Nov;96(1-2):161-72.
Effects of amygdaloid lesions, hippocampal lesions, and buspirone on black-white exploration and food carrying in rats.

Dringenberg HC, Kornelsen RA, Pacelli R, Petersen K, Vanderwolf CH.

University of Western Ontario, London, Canada.

Unlesioned rats exploring a black-white two compartment box spent most of the time in the covered, black half of the box and only little time in the uncovered, white half (67 s/5 min). Large radio-frequency lesions of the amygdala or hippocampus did not alter this pattern of exploration, but rats with hippocampus lesions were more active than the other two groups of rats. Treatment with the 5-HT1A receptor agonist buspirone (0.1 mg/kg, s.c.) increased the time that unlesioned rats spent in the uncovered compartment (103 s), an effect that was less pronounced in hippocampus-lesioned rats and completely abolished by amygdala lesions. In a food transport test, unlesioned rats that traveled from a home cage to an exposed food source consumed small and medium-sized pellets immediately at the food source. Larger pellets, however, were carried back to the home cage for consumption. Rats with amygdala lesions ate fewer pellets at the food source and tended to carry more pellets back to the home cage for consumption than unlesioned rats. Rats with hippocampus lesions carried fewer pellets back to the home cage and ate more pellets at the food source. Buspirone (0.5-1.5 mg/kg, s.c.) reduced the carrying of large food items to the home cage and increased consumption of these pellets at the food source in all groups of rats. These results suggest that neither the amygdala nor the hippocampus play an important role in controlling exploratory behavior in a black-white compartment box, but that the amygdala may have some role in mediating the effect of buspirone to increase exploration of the white/open compartment. Further, the amygdala and hippocampus have opposing influences on the transport of food items to a shelter, the amygdala




J Neural Transm. 1998;105(6-7):561-73.
Effects of buspirone on plasma neurotransmitters in healthy subjects.

Lechin F, van der Dijs B, Jara H, Orozco B, Baez S, Benaim M, Lechin M, Lechin A.

Section of Psychopharmacology, Instituto de Medicina Experimental, Universidad Central de Venezuela.

Buspirone is an anxiolytic drug which exerts several central effects. It antagonizes presynaptic inhibitory DA2 autoreceptors at dopaminergic neurons and acts as an agonist for 5-HT1A inhibitor autoreceptors at serotonergic cells. Thus, buspirone respectively enhances and depresses the firing rates of both type of neurons. At doses which correlate with dopaminergic stimulation, but not 5-HT inhibition, buspirone also increases the firing rates of the central noradrenergic cells. We measured levels of circulating neurotransmitters before and up to 240 minutes after the oral administration of 20 mg of buspirone in 32 healthy volunteers. Buspirone significantly increased levels of noradrenaline, dopamine, and free serotonin but did not affect levels of adrenaline, tryptophane, or platelet serotonin. Small but significant drops in systolic blood pressure and heart rate were observed after buspirone ingestion. Atropine administration before buspirone ingestion annulled the free serotonin increase as well as systolic blood pressure-heart rate decrease. We found significant positive correlations between noradrenaline and dopamine levels. The strength and significance of these correlations were increased by using the noradrenaline/adrenaline ratio instead of noradrenaline absolute values. This finding indicates that increases in both noradrenaline and dopamine arise from sympathetic nerves rather than the adrenal glands. We also found significant negative correlations between free serotonin increases and systolic blood pressure-heart rate decreases. Our results indicate that buspirone stimulates central sympathetic activity. These acute effects of buspirone are reflected in an increased peripheral neural sympat




Behav Pharmacol. 1997 Jun;8(2-3):174-82.
Effects of chlordiazepoxide, buspirone and cocaine on behavior suppressed by timeout presentation.

van Haaren F, Anderson KG.

Department of Psychology, University of Florida, Gainesville 32611, USA.

Male Wistar rats were exposed to a two-component multiple schedule: a random-interval 30 s schedule of pellet presentation and a conjoint random-interval 30 s schedule of pellet presentation, random-interval 2 s schedule of timeout 10 s presentation. Once responding had stabilized subjects were injected intraperitoneally with vehicle, chlordiazepoxide (1-30 mg/kg), buspirone (0.1-4.2 mg/kg) or cocaine (1-30 mg/kg), 15 min before the start of the experimental session. Before drug administration, punished response rates were less than 30% of unpunished response rates for four of the six subjects, and 60% and 75% for the other two. Low doses of chlordiazepoxide (1 and 3 mg/kg) increased punished responding (range 25-300%), and slightly increased unpunished response rates (by 25% in all but one subject, whose rates increased by 75%). The higher doses of chlordiazepoxide (10-30 mg/kg) dose-dependently decreased response rates in both components. The lower doses of buspirone (0.1 and 0.3 mg/kg) either did not affect, or decreased response rates in both components of the schedule; the higher doses produced dose-dependent decreases. Low doses of cocaine (1, 3 and 5.6 mg/kg) did not affect response rates in either component of the multiple schedule, whereas higher doses produced a dose-dependent decrease in response rates, except for one subject whose punished response rates increased substantially. The behavioral effects of chlordiazepoxide and buspirone observed in the present experiment were similar to those observed in experiments in which response rates were suppressed by shock presentation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9833012&dopt=Abstract buspirone Buspar




J Med Chem. 1995 May 12;38(10):1701-10.
Buspirone analogues as ligands of the 5-HT1A receptor. 1. The molecular structure of buspirone and its two analogues.

Chilmonczyk Z, Les A, Wozniakowska A, Cybulski J, Koziol AE, Gdaniec M.

Pharmaceutical Research Institute, Warszawa, Poland.

An interdisciplinary (X-ray, 1H and 13C NMR, IR, and theoretical quantum mechanical) study on the potent 5-HT1A receptor ligand buspirone (1) and its two structural analogues, mesmar (4,4-dimethyl-1-[4-[4-(2-quinolinyl)-1-piperazinyl]butyl]-2,6- piperidinedione) (2) and kaspar (8-[4-[4-(2-quinolinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane - 7,9-dione) (3), has been reported. The results have shown that buspirone-like molecules should appear in an extended rod-shape form, possessing several potential interaction sites with the receptor.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7752194&dopt=Abstract buspirone Buspar




Neuropharmacology. 1994 Dec;33(12):1597-605.
The interaction of serotonin depletion with anxiolytics and antidepressants on reticular-elicited hippocampal RSA.

Zhu XO, McNaughton N.

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

Hippocampal rhythmical slow activity (RSA) can be elicited by stimulation of the midbrain reticular formation. Buspirone, chlordiazepoxide and imipramine are all anxiolytic and have all been shown to decrease the frequency of RSA. All these compounds have been suggested to affect, directly or indirectly, 5-HT metabolism and function. The present experiments tested the possibility that buspirone, chlordiazepoxide and imipramine reduce RSA frequency via 5-HT1A autoreceptors. Rats received buspirone (10 mg/kg), chlordiazepoxide (5 mg/kg) and imipramine (30 mg/kg) after 5-HT depletion with p-chlorophenylalanine (pCPA, 100 mg/kg/day for 3 days or 350 mg/kg/day for 2 days) or after pretreatment with 5-HTP (40 mg/kg, to replete 5-HT) as well as pCPA. The frequency-reducing effects produced by buspirone and chlordiazepoxide were unchanged by either dose of pCPA, whereas the frequency-reducing effect of imipramine was completely eliminated by the high dose of pCPA. Pindolol, but not beta-blockers (a combination of metoprolol and ICI118,551), was able to block the effect of imipramine on RSA frequency. Pindolol has been reported to block the effects of buspirone but not chlordiazepoxide. These data suggest that: (1) buspirone obtains its frequency-reducing effects via pre- or post-synaptic 5-HT1A receptors rather than 5-HT1A autoreceptors; (2) chlordiazepoxide obtains its frequency-reducing effect via benzodiazepine receptors and GABA with no direct or indirect involvement of 5-HT systems; and (3) imipramine obtains its frequency-reducing effect by increasing the availability of 5-HT at 5-HT1A receptors which are not autoreceptors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7760982&dopt=Abstract buspirone Buspar