The effects of adenosine A1 and A2 receptors on catalepsy were studied in mice. The adenosine agonists 5-N'-ethylcarboxamide-adenosine (NECA), N6-phenylisopropyladenosine (PIA) and N6-cyclohexyladenosine (CHA) induced dose dependent catalepsy. The A1 adenosine antagonist 8-phenyltheophylline (8-PT) potentiated catalepsy induced by NECA, R-PIA and CHA. However, theophylline did not potentiate but inhibited the responses induced by NECA, R-PIA and CHA. Neither 8-PT nor theophylline alone has any effect on catalepsy in mice. It is concluded that catalepsy induced by the adenosine agonists may be due to A2 receptor stimulation and that the A1 antagonism may potentiate the response.

In this study, the influences of GABA(B) agents on antidepressant-induced antinociception in the mouse formalin test have been investigated. The GABA(B) receptor agonist baclofen (2.5, 5 and 10 mg/kg) induced a dose-dependent antinociception in the second phase of the formalin test. This response was inhibited by the GABA(B) receptor antagonist, CGP35348 [P-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid], in a dose-dependent manner. The antagonist by itself also induced antinociception. Single administration of the antidepressants citalopram (10, 20, 40 and 80 mg/kg), desipramine (20, 40, 80 mg/kg) or imipramine (10, 20 and 40 mg/kg) also induced antinociception in both phases of the formalin test. CGP35348 (100 and 200 mg/kg) pretreatment reduced the response induced by the tricyclic antidepressants. A combination of baclofen with the tricyclic antidepressant did not potentiate antinociception induced by antidepressants, but a decrease in the response induced by higher dose of baclofen was shown. It is concluded that GABA mechanism(s) may modulate the antidepressant-induced antinociception.

Abstract:In this study, the influences of nicotinic receptor agents on baclofen-induced antinociception in the tail-flick test have been studied. Intraperitoneal administration of baclofen (2.5, 5 and 10 mg/kg) to mice induced a dose-dependent antinociception in the tail-flick test. Subcutaneous injection of nicotine (0.5-2.5 mg/kg) also caused a dose-dependent antinociceptive response. Intracerebral (10 and 20 pg/mouse) but not intraperitoneal administration of hexamethonium (5 and 10 mg/kg) to mice decreased the response of both nicotine and baclofen. However, administration of the GABAB antagonist CGP 35348 (100 and 200 mglkg) decreased the response induced by baclofen but not by nicotine. It is concluded that at least part of the baclofen-induced antinociception may be mediated through a nicotinic mechanism.It is well-established that y-amino butyric acid (GABA) is an important inhibitory synaptic transmitter in the vertebrate central nervous system. GABA receptors in the brain have been classified as GABAA and GABAB (Bowery et ul. 1980(Bowery et ul. & 1981Hill & Bowery 1981). Whereas GABAA receptors are directly associated with C1-channels, the GABAs receptors seem to be G-protein coupled and linked to Ca' ' or K' channels (Bormann 1988). A third class of GABA binding site, the GAB& sites, resembles the GA-BAA receptor but is insensitive to bicuculline (Drew et al. 1984: Johnston 1996.Baclofen is a derivative of GABA (DeFeudis 1977; Johnston 1978) and the prototype GABAB agonist (Bowery 1982). The drug has major clinical use as an antispastic agent (Young & Delwaide 1981), reduces pain associated with spasticity (Pinto et al. 1972), and is useful in the treatment of trigeminal neuralgia (Fromm et al. 1984).In rodent studies, baclofen can produce antinociception in a variety of tests (Sawynok 1987; Zarrindast & Moghadampour 1991;Sabetkasai et al. 1999), but the mechanism by which this occurs is only partially understood. It has been shown that baclofen depresses the firing rate of dopamine neurones in the substantia nigra and in the ventral tegmental area (Olpe et al. 1977(Olpe et al. & 1978 electrophysiological studies have established that nicotine causes an excitation of neurones in the ventral tegmental area (Grenhoff et al. 1986;Mereu et al. 1987). Nicotinic receptor stimulation enhances the release of dopamine from the limbic system (Imperato et al. 1986) and striatal slices (Goodman 1974; Giorguieff et al. 1979).Nicotinic (Martin et al. 1983) and cholinergic (Iwamoto 1989; mechanisms have been suggested to be involved in the antinociception. However, whereas the role of monoamines in baclofen analgesia (Sawynok 1987) have been demonstrated, the role of nicotinic receptor mechanism(s) in baclofen antinociception has not been evaluated.In the present work, the effects of the nicotinic agents on baclofen-induced antinociception in the tail-flick test has been examined. Materials and MethodsAnimals. Male albino mice (25-30 g) were used in the experiments. Animals were housed in plastic cages in an an...

In the present study, the effects of adrenoceptor agonists and antagonists on baclofen-induced antinociception was investigated. Intraperitoneal administration of different doses of baclofen (2.5, 5 and 10 mg/kg) induced antinociception in the tail-flick test. The response was dose-dependent. The a2-adrenoceptor agonist, clonidine, increased, while the a'-adrenoceptor agonist, phenylephrine, decreased the baclofen response. In reserpine-treated animals, a,-adrenoceptor, clonidine, induced antinociception and increased that of baclofen. Yohambine and propranolol but not prazosin decreased the baclofen effect. Although phenoxybenzamine itself induced antinociception it did not alter the baclofen response significantly. Reserpine treatment decreased the response induced by single administration of baclofen or phenoxybenzamine and that induced by a combination of baclofen with either phenoxybenzamine or prazosin. It may be concluded that a2-adrenoceptor stimulation increases, while a'-adrenoceptor activation decreases the baclofen-induced antinociception, and aminergic mechanism(s) may have a positive influence on baclofen response.