effects of buspirone on punished behavior of pigeons .........1987

[Guest guest]

http://jpet.aspetjournals.org/cgi/content/abstract/243/3/970

Behavioral studies with anxiolytic drugs. IV. Serotonergic

involvement in the effects of buspirone on punished behavior of

pigeons

JM Witkin, RS Mansbach, JE Barrett, GT Bolger, P Skolnick and B

Weissman

Department of Psychiatry, Uniformed Services University of the Health

Sciences, Bethesda, land.

Interactions of the nonbenzodiazepine anxiolytic, buspirone, with

serotonin (5-HT) were studied using behavioral and neurochemical

procedures. Punished responding was studied in pigeons as this

behavior is a generally acknowledged preclinical predictor of

anxiolytic activity and because buspirone increases punished

responding of pigeons with greater potency and efficacy than in other

species. Keypeck responses were maintained under either fixed-

interval or fixed-ratio schedules of food presentation; every 30th

response produced a brief electric shock and suppressed responding

(punishment). Buspirone (0.1- 5.6 mg/kg i.m.) produced dose-related

increases in punished responding which reached a maximum at 1 mg/kg.

A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-

HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects

of buspirone without having behavioral effects of their own. The

characteristics of [3H]-5-HT binding in pigeon brain membranes were

similar to results reported in mammalian brain. Neither buspirone, MJ-

13805 (gepirone, a related analog), nor MJ- 13653 (a buspirone

metabolite), significantly affected [3H]-5-HT binding and none of the

compounds appreciably inhibited uptake of [3H]- 5-HT into pigeon

cerebral synaptosomes. Hill coefficients significantly less than

unity for all drugs except 5-HT suggested multiple serotonergic

binding sites for buspirone and analogs. Buspirone and MJ- 13805 (1

nM) inhibited [3H]ketanserin binding (a measure of 5-HT2 binding

sites) in pigeon cerebrum with Ki values above 10(-6) M. The number

of [3H]ketanserin binding sites was estimated to be 109 fmol/mg of

protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat

cerebrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 243, Issue 3, pp. 970-977, 12/01/1987

Copyright © 1987 by American Society for Pharmacology and

Experimental Therapeutics

[Guest guest]

http://jpet.aspetjournals.org/cgi/content/abstract/243/3/970

Behavioral studies with anxiolytic drugs. IV. Serotonergic

involvement in the effects of buspirone on punished behavior of

pigeons

JM Witkin, RS Mansbach, JE Barrett, GT Bolger, P Skolnick and B

Weissman

Department of Psychiatry, Uniformed Services University of the Health

Sciences, Bethesda, land.

Interactions of the nonbenzodiazepine anxiolytic, buspirone, with

serotonin (5-HT) were studied using behavioral and neurochemical

procedures. Punished responding was studied in pigeons as this

behavior is a generally acknowledged preclinical predictor of

anxiolytic activity and because buspirone increases punished

responding of pigeons with greater potency and efficacy than in other

species. Keypeck responses were maintained under either fixed-

interval or fixed-ratio schedules of food presentation; every 30th

response produced a brief electric shock and suppressed responding

(punishment). Buspirone (0.1- 5.6 mg/kg i.m.) produced dose-related

increases in punished responding which reached a maximum at 1 mg/kg.

A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-

HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects

of buspirone without having behavioral effects of their own. The

characteristics of [3H]-5-HT binding in pigeon brain membranes were

similar to results reported in mammalian brain. Neither buspirone, MJ-

13805 (gepirone, a related analog), nor MJ- 13653 (a buspirone

metabolite), significantly affected [3H]-5-HT binding and none of the

compounds appreciably inhibited uptake of [3H]- 5-HT into pigeon

cerebral synaptosomes. Hill coefficients significantly less than

unity for all drugs except 5-HT suggested multiple serotonergic

binding sites for buspirone and analogs. Buspirone and MJ- 13805 (1

nM) inhibited [3H]ketanserin binding (a measure of 5-HT2 binding

sites) in pigeon cerebrum with Ki values above 10(-6) M. The number

of [3H]ketanserin binding sites was estimated to be 109 fmol/mg of

protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat

cerebrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 243, Issue 3, pp. 970-977, 12/01/1987

Copyright © 1987 by American Society for Pharmacology and

Experimental Therapeutics

[Guest guest]

http://jpet.aspetjournals.org/cgi/content/abstract/243/3/970

Behavioral studies with anxiolytic drugs. IV. Serotonergic

involvement in the effects of buspirone on punished behavior of

pigeons

JM Witkin, RS Mansbach, JE Barrett, GT Bolger, P Skolnick and B

Weissman

Department of Psychiatry, Uniformed Services University of the Health

Sciences, Bethesda, land.

Interactions of the nonbenzodiazepine anxiolytic, buspirone, with

serotonin (5-HT) were studied using behavioral and neurochemical

procedures. Punished responding was studied in pigeons as this

behavior is a generally acknowledged preclinical predictor of

anxiolytic activity and because buspirone increases punished

responding of pigeons with greater potency and efficacy than in other

species. Keypeck responses were maintained under either fixed-

interval or fixed-ratio schedules of food presentation; every 30th

response produced a brief electric shock and suppressed responding

(punishment). Buspirone (0.1- 5.6 mg/kg i.m.) produced dose-related

increases in punished responding which reached a maximum at 1 mg/kg.

A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-

HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects

of buspirone without having behavioral effects of their own. The

characteristics of [3H]-5-HT binding in pigeon brain membranes were

similar to results reported in mammalian brain. Neither buspirone, MJ-

13805 (gepirone, a related analog), nor MJ- 13653 (a buspirone

metabolite), significantly affected [3H]-5-HT binding and none of the

compounds appreciably inhibited uptake of [3H]- 5-HT into pigeon

cerebral synaptosomes. Hill coefficients significantly less than

unity for all drugs except 5-HT suggested multiple serotonergic

binding sites for buspirone and analogs. Buspirone and MJ- 13805 (1

nM) inhibited [3H]ketanserin binding (a measure of 5-HT2 binding

sites) in pigeon cerebrum with Ki values above 10(-6) M. The number

of [3H]ketanserin binding sites was estimated to be 109 fmol/mg of

protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat

cerebrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 243, Issue 3, pp. 970-977, 12/01/1987

Copyright © 1987 by American Society for Pharmacology and

Experimental Therapeutics

[Guest guest]

http://jpet.aspetjournals.org/cgi/content/abstract/243/3/970

Behavioral studies with anxiolytic drugs. IV. Serotonergic

involvement in the effects of buspirone on punished behavior of

pigeons

JM Witkin, RS Mansbach, JE Barrett, GT Bolger, P Skolnick and B

Weissman

Department of Psychiatry, Uniformed Services University of the Health

Sciences, Bethesda, land.

Interactions of the nonbenzodiazepine anxiolytic, buspirone, with

serotonin (5-HT) were studied using behavioral and neurochemical

procedures. Punished responding was studied in pigeons as this

behavior is a generally acknowledged preclinical predictor of

anxiolytic activity and because buspirone increases punished

responding of pigeons with greater potency and efficacy than in other

species. Keypeck responses were maintained under either fixed-

interval or fixed-ratio schedules of food presentation; every 30th

response produced a brief electric shock and suppressed responding

(punishment). Buspirone (0.1- 5.6 mg/kg i.m.) produced dose-related

increases in punished responding which reached a maximum at 1 mg/kg.

A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-

HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects

of buspirone without having behavioral effects of their own. The

characteristics of [3H]-5-HT binding in pigeon brain membranes were

similar to results reported in mammalian brain. Neither buspirone, MJ-

13805 (gepirone, a related analog), nor MJ- 13653 (a buspirone

metabolite), significantly affected [3H]-5-HT binding and none of the

compounds appreciably inhibited uptake of [3H]- 5-HT into pigeon

cerebral synaptosomes. Hill coefficients significantly less than

unity for all drugs except 5-HT suggested multiple serotonergic

binding sites for buspirone and analogs. Buspirone and MJ- 13805 (1

nM) inhibited [3H]ketanserin binding (a measure of 5-HT2 binding

sites) in pigeon cerebrum with Ki values above 10(-6) M. The number

of [3H]ketanserin binding sites was estimated to be 109 fmol/mg of

protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat

cerebrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 243, Issue 3, pp. 970-977, 12/01/1987

Copyright © 1987 by American Society for Pharmacology and

Experimental Therapeutics