Studies on the effects of 5-HT1A antidepressant drugs in the pigeon 1992

[Guest guest]

Research Article

Studies on the effects of 5-HT1A drugs in the pigeon

J. E. Barrett, Ph.D. *

Lederle Laboratories, CNS Research Department, Medical Research

Division, American Cyanamid Company, Pearl River, New York

*Correspondence to J. E. Barrett, Lederle Laboratories, CNS Research

Department, Medical Research Division, American Cyanamid Company,

Pearl River, NY 10965

Keywords

serotonin 5-HT1A receptor • antidepressant • pigeon

Abstract

A number of compounds with high receptor binding affinity for the 5-

hydroxytryptamine (5-HT) receptor subtype designated as 5-HT1A can

produce anxiolytic and/or antidepressant effects in humans. In

contrast to the traditional benzodiazepine anxiolytics, many of the

clinically efficacious 5-HT1A drugs are either ineffective or produce

inconsistent results in traditional preclinical anxiolytic screens

using behavioral procedures with rodents. In preclinical

antidepressant models with these animals, however, effects of the 5-

HT1A drugs, as well as those of traditional antidepressant compounds,

are predictive of their antidepressant activity in humans. In

contrast, 5-HT1A drugs are quite effective in pigeons studied under a

rather conventional punishment or conflict-type procedure that is

also sensitive to the benzodiazepine anxiolytics. However,

traditional antidepressant compounds, such as the tricyclic drugs

amitriptyline and imipramine, as well as the 5-HT reuptake blockers

such as fluoxetine, do not show effects similar to the newer 5-HT1A

drugs in this procedure. Thus, in rodents, current antidepressant

models are sensitive to drugs that appear to function through

different mechanisms, whereas conflict-type procedures typically do

not reveal anxiolytic-like effects with 5-HT1A drugs. The pigeon

conflict procedure, however, discriminates between the 5-HT1A

antidepressants and antidepressant drugs functioning through other

systems, whereas the effects of known anxiolytics in this procedure

are quite similar. Increases in punished responding with 5-HT1A drugs

correlates highly (r= +0.83) with affinity for the 5-HT1A receptor in

pigeons. This paper reviews behavioral studies conducted with the

pigeon in which the focus has been on the analysis of 5-HT1A

compounds and addresses additional work that is required to answer

many of the outstanding questions about this new class of anxiolytic

and/or antidepressant drugs. © 1992 Wiley-Liss, Inc.

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Received: 25 March 1992; Accepted: 27 March 1992

Digital Object Identifier (DOI)

10.1002/ddr.430260309 About DOI

[Guest guest]

Research Article

Studies on the effects of 5-HT1A drugs in the pigeon

J. E. Barrett, Ph.D. *

Lederle Laboratories, CNS Research Department, Medical Research

Division, American Cyanamid Company, Pearl River, New York

*Correspondence to J. E. Barrett, Lederle Laboratories, CNS Research

Department, Medical Research Division, American Cyanamid Company,

Pearl River, NY 10965

Keywords

serotonin 5-HT1A receptor • antidepressant • pigeon

Abstract

A number of compounds with high receptor binding affinity for the 5-

hydroxytryptamine (5-HT) receptor subtype designated as 5-HT1A can

produce anxiolytic and/or antidepressant effects in humans. In

contrast to the traditional benzodiazepine anxiolytics, many of the

clinically efficacious 5-HT1A drugs are either ineffective or produce

inconsistent results in traditional preclinical anxiolytic screens

using behavioral procedures with rodents. In preclinical

antidepressant models with these animals, however, effects of the 5-

HT1A drugs, as well as those of traditional antidepressant compounds,

are predictive of their antidepressant activity in humans. In

contrast, 5-HT1A drugs are quite effective in pigeons studied under a

rather conventional punishment or conflict-type procedure that is

also sensitive to the benzodiazepine anxiolytics. However,

traditional antidepressant compounds, such as the tricyclic drugs

amitriptyline and imipramine, as well as the 5-HT reuptake blockers

such as fluoxetine, do not show effects similar to the newer 5-HT1A

drugs in this procedure. Thus, in rodents, current antidepressant

models are sensitive to drugs that appear to function through

different mechanisms, whereas conflict-type procedures typically do

not reveal anxiolytic-like effects with 5-HT1A drugs. The pigeon

conflict procedure, however, discriminates between the 5-HT1A

antidepressants and antidepressant drugs functioning through other

systems, whereas the effects of known anxiolytics in this procedure

are quite similar. Increases in punished responding with 5-HT1A drugs

correlates highly (r= +0.83) with affinity for the 5-HT1A receptor in

pigeons. This paper reviews behavioral studies conducted with the

pigeon in which the focus has been on the analysis of 5-HT1A

compounds and addresses additional work that is required to answer

many of the outstanding questions about this new class of anxiolytic

and/or antidepressant drugs. © 1992 Wiley-Liss, Inc.

----------------------------------------------------------------------

----------

Received: 25 March 1992; Accepted: 27 March 1992

Digital Object Identifier (DOI)

10.1002/ddr.430260309 About DOI

[Guest guest]

Research Article

Studies on the effects of 5-HT1A drugs in the pigeon

J. E. Barrett, Ph.D. *

Lederle Laboratories, CNS Research Department, Medical Research

Division, American Cyanamid Company, Pearl River, New York

*Correspondence to J. E. Barrett, Lederle Laboratories, CNS Research

Department, Medical Research Division, American Cyanamid Company,

Pearl River, NY 10965

Keywords

serotonin 5-HT1A receptor • antidepressant • pigeon

Abstract

A number of compounds with high receptor binding affinity for the 5-

hydroxytryptamine (5-HT) receptor subtype designated as 5-HT1A can

produce anxiolytic and/or antidepressant effects in humans. In

contrast to the traditional benzodiazepine anxiolytics, many of the

clinically efficacious 5-HT1A drugs are either ineffective or produce

inconsistent results in traditional preclinical anxiolytic screens

using behavioral procedures with rodents. In preclinical

antidepressant models with these animals, however, effects of the 5-

HT1A drugs, as well as those of traditional antidepressant compounds,

are predictive of their antidepressant activity in humans. In

contrast, 5-HT1A drugs are quite effective in pigeons studied under a

rather conventional punishment or conflict-type procedure that is

also sensitive to the benzodiazepine anxiolytics. However,

traditional antidepressant compounds, such as the tricyclic drugs

amitriptyline and imipramine, as well as the 5-HT reuptake blockers

such as fluoxetine, do not show effects similar to the newer 5-HT1A

drugs in this procedure. Thus, in rodents, current antidepressant

models are sensitive to drugs that appear to function through

different mechanisms, whereas conflict-type procedures typically do

not reveal anxiolytic-like effects with 5-HT1A drugs. The pigeon

conflict procedure, however, discriminates between the 5-HT1A

antidepressants and antidepressant drugs functioning through other

systems, whereas the effects of known anxiolytics in this procedure

are quite similar. Increases in punished responding with 5-HT1A drugs

correlates highly (r= +0.83) with affinity for the 5-HT1A receptor in

pigeons. This paper reviews behavioral studies conducted with the

pigeon in which the focus has been on the analysis of 5-HT1A

compounds and addresses additional work that is required to answer

many of the outstanding questions about this new class of anxiolytic

and/or antidepressant drugs. © 1992 Wiley-Liss, Inc.

----------------------------------------------------------------------

----------

Received: 25 March 1992; Accepted: 27 March 1992

Digital Object Identifier (DOI)

10.1002/ddr.430260309 About DOI

[Guest guest]

Research Article

Studies on the effects of 5-HT1A drugs in the pigeon

J. E. Barrett, Ph.D. *

Lederle Laboratories, CNS Research Department, Medical Research

Division, American Cyanamid Company, Pearl River, New York

*Correspondence to J. E. Barrett, Lederle Laboratories, CNS Research

Department, Medical Research Division, American Cyanamid Company,

Pearl River, NY 10965

Keywords

serotonin 5-HT1A receptor • antidepressant • pigeon

Abstract

A number of compounds with high receptor binding affinity for the 5-

hydroxytryptamine (5-HT) receptor subtype designated as 5-HT1A can

produce anxiolytic and/or antidepressant effects in humans. In

contrast to the traditional benzodiazepine anxiolytics, many of the

clinically efficacious 5-HT1A drugs are either ineffective or produce

inconsistent results in traditional preclinical anxiolytic screens

using behavioral procedures with rodents. In preclinical

antidepressant models with these animals, however, effects of the 5-

HT1A drugs, as well as those of traditional antidepressant compounds,

are predictive of their antidepressant activity in humans. In

contrast, 5-HT1A drugs are quite effective in pigeons studied under a

rather conventional punishment or conflict-type procedure that is

also sensitive to the benzodiazepine anxiolytics. However,

traditional antidepressant compounds, such as the tricyclic drugs

amitriptyline and imipramine, as well as the 5-HT reuptake blockers

such as fluoxetine, do not show effects similar to the newer 5-HT1A

drugs in this procedure. Thus, in rodents, current antidepressant

models are sensitive to drugs that appear to function through

different mechanisms, whereas conflict-type procedures typically do

not reveal anxiolytic-like effects with 5-HT1A drugs. The pigeon

conflict procedure, however, discriminates between the 5-HT1A

antidepressants and antidepressant drugs functioning through other

systems, whereas the effects of known anxiolytics in this procedure

are quite similar. Increases in punished responding with 5-HT1A drugs

correlates highly (r= +0.83) with affinity for the 5-HT1A receptor in

pigeons. This paper reviews behavioral studies conducted with the

pigeon in which the focus has been on the analysis of 5-HT1A

compounds and addresses additional work that is required to answer

many of the outstanding questions about this new class of anxiolytic

and/or antidepressant drugs. © 1992 Wiley-Liss, Inc.

----------------------------------------------------------------------

----------

Received: 25 March 1992; Accepted: 27 March 1992

Digital Object Identifier (DOI)

10.1002/ddr.430260309 About DOI