J Clin Psychiatry. 1982 Dec;43(12 Pt 2):34-9.
Intravenous buspirone self-administration in rhesus monkeys.

Balster RL, Woolverton WL.

Rhesus monkeys trained to press levers for intravenous cocaine injections were tested with saline and various doses of buspirone, chlordiazepoxide, and clorazepate. Buspirone was not self-administered at rates significantly above saline control levels. Chlordiazepoxide and clorazepate also failed to serve as reinforcers under these conditions. The lack of reinforcing properties, taken together with the results of other preclinical behavioral studies, suggests a low potential for recreational use of buspirone in man.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6130071&dopt=Abstract buspirone Buspar




J Clin Psychiatry. 1982 Dec;43(12 Pt 2):40-4.
Buspirone: chemistry, pharmacology, and behavior.

Skolnick P, Paul SM.

Recent neurochemical and behavioral observations with the nonbenzodiazepine anxiolytic buspirone raise several issues of importance to neuroscientists. These include: (1) the role of a GABA-benzodiazepine receptor-chloride ionophore complex in the actions of buspirone and other anxiolytics; (2) the involvement of dopaminergic pathways in mediating anxiety and/or anxiolytic actions; and (3) the existence of a common pre- or postreceptor "effector system" for buspirone and other antianxiety agents. These issues are critically discussed in light of recent findings.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6130072&dopt=Abstract buspirone Buspar




Neuropharmacology. 1983 Mar;22(3):273-8.
Selective effects of buspirone and molindone on dopamine metabolism and function in the striatum and frontal cortex of the rat.

McMillen BA, McDonald CC.

The hypothesis that the nerve endings of the dopamine projection of the frontal cortex lack autoreceptors for regulation of tyrosine hydroxylase was tested by using the preferential inhibitors of dopamine autoreceptors, molindole and buspirone. In contrast to haloperidol, which elevates dopamine metabolism in the striatum and frontal cortex, both molindone and buspirone elicited little change in dopamine metabolism in the frontal cortex at doses up to 3.0 mg/kg, which cause the same maximal response in the corpus striatum as does haloperidol. Thus, the lack of autoreceptors in the frontal cortex is of pharmacological importance. That preferential inhibition of striatal dopamine autoreceptors may reverse catalepsy by enhancing synthesis and release of dopamine was tested by first inducing catalepsy with different drugs and then administering molindone or buspirone. Only buspirone (1.0 mg/kg) reversed catalepsy. This effect does not require presynaptic dopamine as catalepsy was reversed by buspirone in the dopamine-depleted rat (with 2.0 mg/kg R04-1284) as well as after postsynaptic dopamine receptor blockade by haloperidol of cis-flupenthixol. Thus, the mechanism for the reversal of catalepsy appears to be located efferent from the dopamine neuron. Buspirone, a non-benzodiazepine anti-anxiety drug, may prove useful for treatment of extrapyramidal motor disorders of either iatrogenic or idiosyncratic origin.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6133232&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1990 Jan;35(1):117-20.
Buspirone blocks the discriminative stimulus effects of apomorphine in monkeys.

Kamien JB, Woolverton WL.

Drug Abuse Research Center, Pritzker School of Medicine, University of Chicago, IL 60637.

Three rhesus monkeys were trained to discriminate apomorphine (APO) from saline in a two-lever, food-reinforced drug discrimination procedure. After acquisition of the discrimination, the monkeys were given various doses of APO in combination with saline or buspirone before test sessions in which responses occurring on either lever were reinforced. Combinations of APO (0.01-0.08 mg/kg, IV) and saline resulted in a dose-related increase from 0 to 100% in the percentage of responses that occurred on the APO-appropriate lever. When buspirone (0.04-0.16 mg/kg, IV) was combined with APO, reductions from 100% to 0% APO-appropriate responding were seen following at least one dose combination in all three monkeys. A parallel shift to the right of the APO dose-response curve with buspirone was evident in 2 monkeys, indicating surmountable antagonism. In one case, a further increase in buspirone dose resulted in an insurmountable antagonism, i.e., increasing APO dose still resulted in primarily saline-appropriate responding. These results suggest that buspirone can function as a D2 dopamine (DA) receptor antagonist at behaviorally relevant doses.

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Eur J Clin Pharmacol. 1983;24(4):463-7.
Comparative effects of a repeated dose regime of diazepam and buspirone on subjective ratings, psychological tests and the EEG.

Bond A, Lader M, Shrotriya R.

Two doses of buspirone (5 and 10 mg tds), 1 dose of diazepam (5 mg tds) and placebo were administered to 8 normal subjects for a period of 8 days. Each subject received each drug in a balanced order with a minimum interval of 1 week between courses. Psychotropic effects were assessed with a battery of physiological, psychomotor and subjective tests on the first, third and last days of treatment both before the first daily dose and at 1 h and 3 h after it. Diazepam showed a characteristic profile of action producing EEG changes and psychological impairment after a single dose which were still present after a week's treatment. Such effects were minimal after buspirone. Both drugs increased subjective ratings of drowsiness but these feelings tended to decrease after a week's treatment on the clinical doses. Buspirone (10 mg tds) produced some unpleasant side-effects initially but tolerance to these invariably developed after 3 days treatment.

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Life Sci. 1983 Jul 18;33(3):269-73.
Buspirone: a potential atypical neuroleptic.

Wood PL, Nair NP, Lal S, Etienne P.

Buspirone produces a dose-dependent but short-lived elevation in striatal dopamine (DA) metabolites in the rat. In vitro, buspirone possesses an affinity similar to sulpiride for DA receptors (3H-spiperone). A moderate affinity for alpha 1 receptors was also observed while buspirone was inactive at alpha 2, beta, muscarinic and serotonin2 receptors. This pharmacological profile as well as previous behavioral data indicate that buspirone may be a potential "atypical" neuroleptic.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6135133&dopt=Abstract buspirone Buspar




Pharmacol Biochem Behav. 1983 Jul;19(1):97-101.
Discriminative stimulus properties of buspirone compared to central nervous system depressants in rats.

Hendry JS, Balster RL, Rosecrans JA.

Two groups of rats were trained to discriminate either IP buspirone from vehicle or IP oxazepam from vehicle using a two-lever FR-10 schedule of sweetened milk presentation. The discrimination in the buspirone group was difficult to establish due to potent response rate decreasing effects. Oxazepam was a very effective stimulus and the discrimination in the oxazepam group was readily established. Tests with oxazepam and pentobarbital in the buspirone group provided no evidence for generalization of the stimulus properties of buspirone to either drug. Tests with buspirone in the oxazepam group also provided no evidence of generalization to buspirone, although tests with pentobarbital indicated almost complete generalization. Finally buspirone and oxazepam were tested in a group of rats previously trained to discriminate pentobarbital from vehicle. The findings supported the data obtained in the buspirone and oxazepam groups, with no indication of generalization from pentobarbital to buspirone, but with complete generalization to oxazepam. These data suggest that buspirone does not share discriminative stimulus properties which are common to other CNS depressants.

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J Neural Transm. 1983;57(4):255-65.
Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug.

McMillen BA, Mattiace LA.

Buspirone is a clinically efficacious anti-anxiety drug without any other benzodiazepine-like activity. Although buspirone can displace ligands for dopamine (DA) receptors, its equipotent analog, MJ-13805, cannot. Buspirone can potently increase dopaminergic impulse flow and metabolism, primarily due to inhibition of DA autoreceptors. However, MJ-13805 does not block striatal nerve ending DA autoreceptors and slightly increases striatal DA metabolism. Both drugs potently reverse catalepsy due to either DA receptor blockade or DA depletion which indicates an effect within the extrapyramidal system efferent from the DA neuron. Amantadine is at least ten fold less potent than these drugs for reversal of catalepsy. These data indicate that altered dopaminergic neurotransmission may not be important for the anti-anxiety effect of buspirone and that buspirone should be tested for efficacy in various models of movement disorders. The site and mechanism of action for buspirone and MJ-13805 remains obscure. A metabolite of buspirone, 1-piperazinylpyrimidine, does not reverse catalepsy although this drug is known to be active in anti-anxiety screening tests. Thus, buspirone may have separate mechanisms of action for reduction of anxiety and reversal of catalepsy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6140299&dopt=Abstract buspirone Buspar