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Modification of dyskinesias following the intrastriatal injection of prostaglandins in the rodent
Author(s) -
Costall Brenda,
Holmes S.W.,
Kelly M. Elizabeth,
Naylor R.J.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb11095.x
Subject(s) - apomorphine , catalepsy , striatum , endocrinology , prostaglandin e , medicine , dopamine , chemistry , pharmacology , prostaglandin , guinea pig , dopaminergic , haloperidol
1 The abilities of prostaglandin E 1 (PGE 1 ), PGE 2 , PGD 2 and PGF 2α to antagonize striatal dopamine function were assessed following bilateral and unilateral injections into the striata of the rat and guinea‐pig. 2 Three tests were used to assess the effects of the bilateral injections, ability to antagonize dyskinetic biting induced by 2‐di‐ n ‐propylamino‐5, 6‐dihydroxytetralin (0.025 mg kg‐ 1 s.c.), ability to antagonize stereotyped behaviour induced by apomorphine (0.5 or 2 mg kg −1 s.c.) and ability to induce catalepsy. Asymmetry/circling behaviour revealed on challenge with apomorphine (0.25 mg kg −1 s.c.) was measured following unilateral injection into the striatum. 3 In the rat, dyskinetic biting induced by 2‐di‐ n ‐propylamino‐5, 6‐dihydroxytetralin was antagonized by PGE 1 (0.001 − 1 μg) and PGE 2 (0.00001 − 1 μg) but not by PGD 2 or PGF 2α (1 μg). Stereotyped behaviour induced by apomorphine was not antagonized by any of the prostaglandins. A weak catalepsy was induced by PGE 1 (1 μg only), PGE 2 (0.001 − 1 μg) and PGD 2 (0.001 − 1 μg) but not by PGF 2α . Asymmetry and circling behaviour was only observed following the unilateral injection into the striatum of PGE 1 and PGD 2 (0.01 − 1 μg) and challenge with apomorphine. 4 In the guinea‐pig the actions of PGE 1 and E 2 were compared with those of PGF 2α . Dyskinetic biting induced by 2‐di‐ n ‐propylamino‐5, 6‐dihydroxytetralin was antagonized by bilateral injections into the striatum of PGE 2 (0.001 − 1 μg), but not PGE, (0.5 μg) and PGF 2α (1 μg) but not PGE, (0.5 μg) and PGF 2α (1 μg). Similar injections of PGE 1 , E 2 and F 2α all failed to antagonize apomorphine‐induced stereotyped behaviour, or to induce catalepsy. PGE 1 (0.01‐0.5 μg) and PGE 2 (0.002 − 1 μg), but not PGF 2α , caused asymmetry following unilateral injection into the striatum and peripheral challenge with apomorphine. 5 It is concluded that the major effect in the striatum of the prostaglandins of the E series is to antagonize dyskinetic biting; this action is not shared by other prostaglandins tested, and does not reflect a generalised ability to antagonize striatal dopamine function. It is suggested that the actions of the prostaglandins to modify differentially dopamine‐dependent behaviours from the striatum may reflect activity at a site subsequent to the dopamine receptor.