Behavioural and ligand-binding studies in rats with 1-acetyl-4-methylpiperazine, a novel nicotinic agonist.

Abstract:

:The novel nicotinic agonist 1-acetyl-4-methylpiperazine (AMP) has been studied in ligand-binding and behavioural studies. AMP methiodide potently inhibited [3H]-(-)-nicotine and [125I]-alpha-bungarotoxin binding to P2 membranes from rat brain and [125I]-alpha-bungarotoxin binding to rat skeletal muscles. AMP HCl also inhibited nicotinic binding, but it was 100 times less potent than AMP methiodide. In behavioural studies, AMP HCl reduced locomotor activity of experimentally naive rats and mecamylamine blocked this effect. In rats receiving (-)-nicotine chronically, AMP HCl did not increase locomotor activity consistently or to the same extent as (-)-nicotine. In rats trained to discriminate (-)-nicotine from saline in a two-bar operant conditioning procedure with food reinforcement, there was generalization to AMP HCl, but only at doses that reduced the overall rate of responding. The potency and effectiveness of AMP relative to (-)-nicotine varied across the different behavioural procedures. The results suggest that the pharmacodynamic action of AMP differs from that of (-)-nicotine and that it usefully extends the range of agonists that can be used as probes for central nicotinic mechanisms.

journal_title

Psychopharmacology

authors

Garcha HS,Thomas P,Spivak CE,Wonnacott S,Stolerman IP

doi

10.1007/BF02251292

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

347-54

issue

3

eissn

0033-3158

issn

1432-2072

journal_volume

110

pub_type

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