Neuroleptic-like profile of the cannabinoid agonist, HU 210, on rodent behavioural models

The present study was performed to assess the effects exerted by the cannabinoid (CB) agonist, ()11-hydroxy-D8-tetrahydrocannabinol-dymethylheptyl (HU 210; 12.5–50 mg/kg ip), on rodent behavioural tests involving dopamine (DA) transmission;in comparison, the DA D2 antagonist, S()-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxy-benzamide hydrochloride(()eticlopride; 50 mg/kg sc), was used. (2) In rats, HU 210, at all doses, potently antagonized penile erection (PE) and stretching–yawning (SY) typically elicited by the DA D2/D3 agonists, 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine (B-HT 920) and±7-hydroxy-N,N-di-n-propylaminotetralin hydrobromide (7-OH-DPAT) both at 100 mg/kg ip. (3) In nonreserpinized mice, HU 210 impairedmotor ability assessed by means of a motor test battery, and B-HT 920 (1 mg/kg ip) worsened the phenomenon. (4) In reserpinized mice, HU210 at 50 mg/kg counteracted the amelioration exerted by B-HT 920 (1 mg/kg ip) on reserpine-induced akinesia. (5) As all these effects weresimilarly displayed by ()eticlopride (50 mg/kg sc), our data suggest a neuroleptic-like profile of acute HU 210 in animal behavioural tests.