Role of 5-hydroxytryptamine 1a receptors in 6-hydroxydopamine-induced catalepsy-like immobilization in rats: a therapeutic approach for treating catalepsy of parkinson's disease

We have shown that buspirone, a partial agonist of 5-hydroxytryptamine 1A [5-HT[1A]] receptors, improves motor dysfunctions induced by 6-hydroxydopamine [6-OHDA] and haloperidol in rats. The present work extends these findings by investigating the role of 5-HT[1A] receptors on catalepsy-like immobilization in rats, a model of Parkinson's disease. Catalepsy was induced by unilateral infusion of 6-OH-dopamine [8 micro g/2 micro L/rat] into the central region of the substantia nigra, compact part [SNc] and assayed by bar-test method 5, 60, 120 and 180 min after the drugs administration. The involvement of 5-HT[1A] receptors in 6-OHDA-induced catalepsy was studied through intraperitoneal [0.25, 0.5 and 1mg/Kg IP] and intrasubstantia nigra, compact part [10 micro g/rat, intra-SNc] injection of 8-hydroxy-2-[di-n-propylamino] tetralin [8-OHDPAT] as well as administration of 1-[2-methoxyphenyl]-4-[4-[2-pthalimmido] butyl] piperazine hydrobromide [0.1, 0.5 and 1 mg/Kg, NAN-190, IP]. NAN-190 [1 mg/Kg, IP] and 8-OHDPAT [1 mg/Kg, IP and 10 micro g/rat, intra-SNc] increased and decreased 6-OHDA-induced catalepsy respectively. In normal [non 6-OHDA-lesioned] rats, NAN-190 [1 mg/Kg, IP] increased the elapsed time in bar-test while 8-OHDPAT did not produce any significant effect. The anticataleptic effect of 8-OHDPAT [1 mg/Kg, IP] was reversed markedly by co-injection with NAN-190 [1 mg/Kg, IP]. These findings suggest that 5-HT1A receptors are involved in 6-OHDA-induced catalepsy-like immobilization

Buspirone attenuates tolerance to analgesic effect of morphine in mice with skin cancer

Adjuvant drugs that can delay tolerance to morphine analgesia may lead to improved management of pain in chronic disease such as cancer. This study was aimed to investigate effect of buspirone, as a partial agonist of 5-HT[1A] receptor, on tolerance induced to morphine analgesic effect in animals with skin cancer. Study was carried on female Swiss albino mice. For skin tumorigensis, mice were treated with single dose of 7,12-dimethylbenz [a] anthracene [DMBA] and promoted by multiple dose of croton oil. Tolerance to morphine analgesia was induced by daily subcutaneous [sc] injection of morphine [5mg/kg for 30 days] and assayed by using the hot plate method. Results obtained from this study showed that pain threshold in mice with skin cancer were significantly lower. Tolerance to analgesic effect of morphine [5 mg/kg, sc] was appeared at day 15, whereas, in normal and skin tumor bearing mice co-treated daily with morphine [5 mg/kg, sc] and three different intraperitoneal [ip] doses of buspirone [5, 7.5 and 10 mg/kg] tolerance was observed at days 25 and 30. In conclusion our data indicate that concurrent use of morphine with buspirone may produce good cancer pain control and attenuate development of tolerance