Neurosci Lett. 1985 Jan 21;53(2):191-5.
Autoradiographic localization of [3H]buspirone binding sites in rat brain.

Kaulen P, Bruning G, Schneider U, Baumgarten HG.

Binding sites for [3H]buspirone were identified on sections from rat brain by light microscopic autoradiography. Incubated sections were processed by the Ultrofilm as well as the coverslip method. Highest densities of [3H]buspirone binding were localized in the caudate/putamen, nucleus accumbens septi, olfactory tubercle and in the glomerula of the olfactory bulb. This distribution pattern is different from any serotonin receptor but fits well with that of dopamine receptors. Therefore, this study supports the hypothesis that buspirone acts, at least partially, on dopamine receptors.

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J Pharm Pharmacol. 1982 May;34(5):314-7.
Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system.

Kolasa K, Fusi R, Garattini S, Consolo S, Ladinsky H.

Buspirone, a novel psychotropic anxioselective agent, produced a dose-dependent decrease in the level of acetylcholine in the striatum of the rat. The maximum effect of about 25-30% was produced at the dose of 20 mg kg-1. A smaller decrease of 10% was also found in the n. accumbens-olfactory tubercle while other brain regions were unaffected. The drug did not alter striatal choline acetyltransferase or acetylcholinesterase activities and was feeble in displacing [3H]dexetimide from its specific muscarinic binding sites. The effect of buspirone in lowering acetylcholine content was more marked and longer lasting in the striatum of female than male rats. Buspirone proved to be weak as a blocker of the dopamine receptor agonist, apomorphine, and it appears that only a small proportion of the decrease in striatal acetylcholine content can be attributed to the blockade of dopamine receptors. Rapid homologous tolerance to an acute challenge with buspirone on striatal acetylcholine was achieved within seven days of its chronic administration, and, unlike clozapine, a cross tolerance of buspirone to chronic haloperidol treatment was also observed. Other data indicating that the drug differed from haloperidol both qualitatively and quantitatively on dopaminergic neurochemical parameters, and the fact that it is not cataleptogenic, suggest that buspirone cannot be considered a typical neuroleptic agent. The possibility that buspirone may act as an agonist at certain presynaptic dopamine receptors, which could translate into a fall in striatal acetylcholine content, is discussed.

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Clin Pharmacol Ther. 1982 Aug;32(2):201-7.
Effects of alcohol on buspirone and lorazepam actions.

Seppala T, Aranko K, Mattila MJ, Shrotriya RC.

Psychomotor and psychologic effects of single doses of buspirone (10 and 20 mg) and lorazepam (2.5 mg) alone or combined with alcohol (1 gm/kg) were investigated in 12 healthy young men (crossover study). Lorazepam alone impaired psychomotor skills (tracking, body balance, extraocular muscle balance, and flicker recognition), the effects being maximal at 180 min. This impairment was not subjectively perceived by the subjects. Neither dose of buspirone alone impaired objective measurements, although buspirone, especially in the 20-mg dose, was felt to cause drowsiness, weakness, and faintness. Lorazepam, but not buspirone, interacted with alcohol.

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Psychopharmacology (Berl). 1982;78(1):49-53.
Effect of buspirone on rat plasma prolactin levels and striatal dopamine turnover.

Meltzer HY, Simonovic M, Fang VS, Gudelsky GA.

Buspirone, an effective antianxiety compound, produced a dose-dependent, relatively prolonged increase in rat plasma prolactin (PRL) levels. The stimulation of PRL secretion by buspirone was additive with the effect of alpha-methyl-p-tyrosine (AMPT) or gamma-butyrolactone. In vitro, buspirone itself had no effect on the release of PRL from rat pituitary glands but it blocked the inhibitory action of dopamine (DA). Buspirone also increased DA turnover in the striatum as measured by the AMPT-induced depletion of striatal DA levels. These results demonstrate the ability of buspirone to block pituitary and striatal DA receptors.

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Prog Neuropsychopharmacol Biol Psychiatry. 1990;14(2):223-36.
The long-term effects of diazepam, lorazepam, and buspirone on behavioral suppression by a shock signal.

Davidson TL.

Virginia Military Institute, Lexington.

1. Two experiments examined the long-term effects of treatment with buspirone (a nonbenzodiazepine anxiolytic), diazepam, or Lorazepam (two pharmacokinetically distinct benzodiazepines) on the capacity of a shock cue to disrupt appetitively conditioned behavior. 2. In Experiment 1, rats were injected with diazepam (5 mg/kg), buspirone (1.5 mg/kg or .75 mg/kg), or saline shortly before each of 12 bar press training sessions. Injections were suspended and three days later the rats received five days of Pavlovian fear conditioning (bars removed) in which a tone signaled shock. The capacity of the tone to disrupt bar pressing was then assessed. 3. Bar pressing of rats previously injected with diazepam was more suppressed by the shock cue than that of rats previously injected with buspirone or saline. The long-term effects of buspirone and saline did not differ. 4. In Experiment 2, Lorazepam had effects different from diazepam during bar press training. Nonetheless, rats previously injected with Lorazepam were also more disrupted by a shock cue than were controls. 5. The results suggest that one long-term consequence of treatment with benzodiazepines may be hypersensitivity to behavioral disruption by stimuli that presumably elicit fear or anxiety.

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J Clin Psychiatry. 1982 Dec;43(12 Pt 2):11-8.
Pharmacology and neurochemistry of buspirone.

Riblet LA, Taylor DP, Eison MS, Stanton HC.

Biochemically, buspirone is unlike the benzodiazepines in that it neither stimulates nor inhibits 3H-benzodiazepine binding, does not affect the influence of GABA or halide anion on 3H-benzodiazepine binding, and does not interfere with GABA binding or uptake. Buspirone lacks anticonvulsant activity, interacts minimally with CNS depressants, and does not cause muscle relaxation. Its tranquilizing activity is characterized by the ability to (1) tame aggressive rhesus monkeys, (2) block conditioned avoidance responding in the rat, (3) inhibit shock-induced fighting in the mouse, and (4) attenuate shock-induced suppression of drinking in the rat. In vitro binding experiments indicate that buspirone lacks significant activity at several binding sites. It appears to interact only with the dopaminergic system and possesses properties that are similar to both dopamine agonists and dopamine antagonists.

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J Clin Psychiatry. 1982 Dec;43(12 Pt 2):19-24.
Notes on buspirone's mechanisms of action.

Garattini S, Caccia S, Mennini T.

Buspirone is a novel psychotropic drug with clear anxiolytic activity in man. There are a number of neurochemical differences between buspirone and both neuroleptics and benzodiazepines. Moreover, buspirone is extensively metabolized, and several metabolites are present in the brain together with the parent compound. One of these, 1-PP, is present in the brain at higher concentrations than the parent drug, particularly when the drug is given orally. On the basis of the reported experimental data, it can be postulated that buspirone's anticonflict activity in rats may be mediated, at least partially, through 1-PP, without involving any effect on the dopaminergic system. The possibility that buspirone and 1-PP may mimic the action of benzodiazepine on some sites in the complex benzodiazepine-GABA receptors is discussed.

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J Clin Psychiatry. 1982 Dec;43(12 Pt 2):25-33.
Effects of buspirone on operant behavior of laboratory rats and cynomolgus monkeys.

Geller I, Hartmann RJ.

Rats trained on an avoidance-escape task were administered buspirone in doses ranging from 0.5 to 7.5 mg/kg. Low doses disrupted avoidance responding without impairing escape responding. Rats trained on an experimentally induced conflict procedure were also administered buspirone or diazepam (1.0 to 5.0 mg/kg). Buspirone and diazepam appeared to be equipotent as anxiolytics. Cynomolgus monkeys, also trained on the experimentally induced conflict task, were given intramuscular buspirone or diazepam (0.5 to 5.0 mg/kg). Both drugs produced an attentuation of conflict, further supporting the anxiolytic equipotency of buspirone and diazepam. The long duration of action of buspirone suggests the presence of at least one active metabolite.

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