Psychopharmacology (Berl). 1990;100(3):393-8.
Buspirone impairment of performance of passive avoidance and spatial learning tasks in the rat.

Rowan MJ, Cullen WK, Moulton B.

Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland.

The effects of buspirone on the execution of step-through passive avoidance and spatial navigation learning tasks were assessed. In view of the anxiolytic properties of the drug, its effects on shock induced ultrasonic vocalizations and shock suppressed locomotor activity in a hole-board were also determined. Doses (0.5, 1 and 2 mg/kg, IP) which did not affect exploratory activity in a novel environment (light/dark box and hole-board apparatus) were used. Buspirone (1 and 2 mg/kg) impaired performance on the 24 h passive avoidance recall test when given prior to the training and the test sessions or prior to the test session only but not when given before the training trial only. The stress response to the mild footshock, as measured in terms of suppressed locomotor activity in the hole-board apparatus and post-shock ultrasonic vocalizations, was reduced by buspirone (at 1 and 2 mg/kg, respectively), indicating that its effect on behavior in the passive avoidance learning task is probably due to its anxiolytic properties. Evidence for a possible amnesic effect of buspirone (2 mg/kg) was found on the acquisition and probe test trials in the spatial navigation task. During training the latency to find a submerged escape platform in a water maze was increased. Performance on a probe test was also impaired but this effect was not apparent in animals which had received buspirone only prior to the probe test. Although these changes may be attributable to alterations in many aspects of cognitive processing, the possibility of a direct effect on memory warrants further investigation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2315436&dopt=Abstract buspirone Buspar




Psychopathology. 1984;17 Suppl 3:61-8.
Clinical studies of buspirone.

Schuckit MA.

This literature review addresses two related questions: Is buspirone as clinically effective an antianxiety agent as the benzodiazepines? And does buspirone offer any safety advantages? Data from over 1,000 anxious outpatients reveal that an average dose of 20 mg of buspirone/day appears to be as effective an antianxiety agent as comparable doses of diazepam or clorazepate in both acute and more chronic administration studies. Buspirone appears to cause less clinically significant impairment in cognition or motor performance, is less likely to potentiate the effects of brain depressants like alcohol, has little if any abuse liability, and produces no clinically identifiable physical abstinence syndrome when discontinued after long-term administration. While the final answer on the clinical usefulness and side effect profile of this interesting drug awaits the results of its use in divergent clinical settings, this new antianxiety agent appears to be equally effective in treating anxiety but is safer than the benzodiazepines.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6150509&dopt=Abstract buspirone Buspar




Psychopharmacology (Berl). 1990;100(4):485-90.
Conditioned taste aversion and place preference with buspirone and gepirone.

Neisewander JL, McDougall SA, Bowling SL, Bardo MT.

Department of Psychology, University of Kentucky, Lexington 40506.

The effects of the nonbenzodiazepine anxiolytics buspirone and gepirone were compared to diazepam at 1, 3, and 10 mg/kg using the conditioned taste aversion (CTA) paradigm. Buspirone and gepirone produced stronger CTA than diazepam (3 and 10 mg/kg) across repeated conditioning trials, indicating that these nonbenzodiazepine anxiolytics may have stronger aversive properties than diazepam. The effects of buspirone and gepirone (1 and 3 mg/kg) were also assessed using the conditioned place preference (CPP) paradigm. Both buspirone (1 and 3 mg/kg) and gepirone (3 mg/kg only) produced CPP, indicating that these drugs may have rewarding properties, and that buspirone is more potent than gepirone in producing CPP. These findings demonstrate that buspirone and gepirone have affective properties similar to abused drugs, and may therefore have abuse potential. It was also demonstrated that buspirone (3 mg/kg), but not gepirone (3 mg/kg), increased dopamine (DA) synthesis in the nucleus accumbens, a mesolimbic brain area thought to be involved in drug reward.

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J Clin Psychiatry. 1982 Dec;43(12 Pt 2):4-10.
Buspirone: chemical profile of a new class of anxioselective agents.

Temple DL Jr, Yevich JP, New JS.

Buspirone is a lipophilic, dibasic heterocyclic with no structural resemblance to other anxiolytic or antipsychotic agents. Neurochemical binding studies suggest that buspirone has both dopamine agonist and antagonist properties. Structural comparisons with (+)-butaclamol indicate that buspirone possesses features required for binding at the postsynaptic dopamine receptor site. This is consonant with the drug's biologic properties, but does not define a mechanism for its anxioselective action. The transient antipsychotic effect associated with peak blood levels of buspirone in rats was consistent with such an effect, predicted by [3H]spiperone binding studies. The low (20 mg) anxioselective dose, acting in concert with extensive metabolism in humans, produces low blood levels of the parent drug, suggesting that buspirone's effect is exerted through interactions with a high-affinity, low-threshold receptor system.

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Xenobiotica. 1983 Mar;13(3):147-53.
Disposition and metabolism of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in the rat.

Caccia S, Muglia M, Mancinelli A, Garattini S.

After i.v. injection (10 mg/kg) to rats, buspirone is rapidly cleared from blood with a t1/2 (beta) or 30 min. After the same dose is given orally, the drug is not detectable in blood or brain within the limits of sensitivity of the method. The metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) has a longer t1/2 than buspirone. It is present to about the same extent in rat plasma and brain after either i.v. or p.o. buspirone. Unlike buspirone, 1-PP accumulates in the brain reaching concentrations between four-and five times those in plasma. Its brain AUC is higher than that of buspirone even when buspirone is given i.v. The results suggest that 1-PP may contribute to the pharmacological effect of the parent drug.

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Biochem Pharmacol. 1983 Mar 15;32(6):1069-74.
Dopaminergic effects of buspirone, a novel anxiolytic agent.

Cimino M, Ponzio F, Achilli G, Vantini G, Perego C, Algeri S, Garattini S.

The novel anxiolytic drug buspirone raised striatal levels of the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) 1 hr after oral administration. This effect was dose-dependent with a peak at 60 min. No changes were observed in the levels of 3-methoxytyramine (3MT), the extraneuronal metabolite of dopamine. Noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were not affected. Buspirone displaced [3H]spiroperidol from striatal binding sites, with an IC50 (1.8 x 10(-7) M), comparable to that of clozapine (IC50 = 1.4 x 10(-7) M) but considerably lower than that of haloperidol (4.7 x 10(-9) M). Buspirone was only a weak inhibitor of dopamine-stimulated adenyl cyclase. Buspirone was not active on the binding of trifluoperazine to calmodulin and did not modify calmodulin-induced activation of phosphodiesterase (PDE). Repeated administration of buspirone did not increase the number of DA receptors. These data show that, although buspirone has antidopaminergic activity, it can hardly be classified as a classic neuroleptic agent.

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Mol Pharmacol. 1990 Feb;37(2):231-7.
Receptor reserve for 5-hydroxytryptamine1A-mediated inhibition of serotonin synthesis: possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists.

Meller E, Goldstein M, Bohmaker K.

Millhauser Laboratories, Department of Psychiatry, New York University Medical Center, New York 10016.

The irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was used to determine the relationship between receptor occupancy and response at central 5-hydroxytryptamine1A (5-HT1A) serotonin receptors mediating the inhibition of serotonin synthesis in rat cortex and hippocampus. Rats were treated with vehicle or EEDQ (2 or 6 mg/kg) and 24 hr later dose-response curves were constructed for inhibition of 5-hydroxytrytophan (5-HTP) accumulation (after decarboxylase inhibition with NSD-1015) by the selective 5-HT1A agonists 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) (0.01-3 mg/kg), buspirone (0.1-7.5 mg/kg), and ipsapirone (0.1-6.25 mg/kg) and the 5-HT1A agonist/antagonist BMY 7378 (0.015-5 mg/kg). In vehicle-pretreated rats, a similar maximal inhibition of 5-HT synthesis (range, 52-59%) was observed in both brain areas with 8-OH-DPAT, buspirone, and ipsapirone. These three agonists were also more potent in reducing 5-HTP accumulation in the cortex than in the hippocampus (ED50, 8-OH-DPAT, 14 and 30 microgram/kg; buspirone, 0.42 and 0.63 mg/kg; ipsapirone, 0.44 and 1.26 mg/kg, respectively). In the cortex, EEDQ treatment shifted the dose-response curves for 8-OH-DPAT, buspirone, and ipsapirone 8.6-, 2.0-, and 2.8-fold to the right, respectively. Corresponding rightward shifts in the hippocampus were smaller, 6.0-, 1.6-, and 2.1-fold, respectively. The EEDQ-induced shifts in the dose-response curves were accompanied by reductions in maximal response. In contrast, whereas the maximal inhibition of cortical 5-HTP accumulation by BMY 7378 (55%) was similar to that obtained with the agonists, maximal response in the hippo




Arch Int Pharmacodyn Ther. 1986 Jan;279(1):40-9.
Neurochemical effects of buspirone in rat hippocampus: evidence for selective activation of 5HT neurons.

Mennini T, Gobbi M, Ponzio F, Garattini S.

The effect of buspirone on neurotransmitter systems in rat hippocampus has been evaluated in vitro and in vivo. In vitro buspirone does not affect the specific binding of 3H-flunitrazepam, 3H-GABA, 3H-dexetimide, but displaces 3H-5HT binding with nanomolar affinity. Oral administration of buspirone does not modify the hippocampal concentrations of GABA, acetylcholine, choline and of 3H-flunitrazepam specifically bound in vivo, but results in a dose-dependent reduction of 5HIAA and noradrenaline concentrations. While the effect on noradrenaline is also obtained in striatum of buspirone-treated animals, the effect on 5HIAA shows a regional specificity. The in vitro and in vivo data suggest that buspirone specifically activates 5HT neurons in hippocampus, and are compared with those obtained with diazepam.

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