Antipsychotic-like profile of combined treatment with raclopride and 8-OH-DPAT in the rat: Enhancement of antipsychotic-like effects without catalepsy.

• The administration of the 5-HT1A agonist 8-OH-DPAT,0.1 mg kg- 1 sc - - 20 min, produced a moderate suppression of conditionedavoidance behavior (60% of controls) in the rat. This effect, however, was notseen after administration of higher doses, 0.4 and 1.6 mg kg- 1 sc. The numberof intertrial crosses were not affected by the lower dose but significantly increasedby administration of the two higher doses of 8-OH-DPAT. The dopamineD 2 receptor blocking agent raclopride, 0.05 mgkg-t, by itself did notsuppress the avoidance behavior, but in combination with 8-OH-DPAT producedsuppression of avoidance behavior (30% of controls) as well as intertrialcrosses. Open field locomotor activity was suppressed by raclopride,0.1 mg kg- 1 sc, or by 8-OH-DPAT, 0.1 mg kg- 1 sc. The combined treatmentproduced a further suppression of locomotor activity and a marked increasein "immobility" (stationary movements). Treadmill locomotion, however, wasnot affected by either compound by itself, whereas the combined treatmentimpaired treadmill performance. Suppression of treadmill performance by ahigher dose of raclopride, 0.4mgkg-~sc, was not altered by the additionaltreatment with 8-OH-DPAT, 0.1 mg kg- 1. In contrast to the additive effects of8-OH-DPAT and raclopride on conditioned avoidance behavior, open fieldlocomotion and treadmill performance, the catalepsy produced by raclopride,16mgkg -1 was completely antagonised by treatment with 8-OH-DPAT0.1 mg kg-1. Taken together, the present findings demonstrate strong interactionsbetween a 5-HT agonist and a DAD 2 antagonist on some critical testsfor antipsychotic-like actions and extrapyramidal motor effects in rats, andsuggest new possibilities in the search for new antipsychotic drugs with higherclinical efficacy and less extrapyramidal side effects. 

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Keyword

Pharmacology

Farmakologi

Pharmacology

Farmakologi

Publication and Content Type

ref (subject category)

art (subject category)