Acute effects of selective serotonin reuptake inhibitors on neuroleptic-induced catalepsy in mice

Depression found in Parkinson disease (PD) usually responds to selective serotonin reuptake inhibitors (SSRIs). Drugs that modify experimental neuroleptic catalepsy (NC) might affect extrapyramidal symptoms in PD. Therefore, the effects of SSRIs on NC were tested in mice, 26-36 g, separated by sex. Catalepsy was induced with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals using a bar test. An SSRI (sertraline, ST; paroxetine, PX; fluoxetine) or vehicle (C) was injected ip 30 min before H. Dunnett's test was used for comparison of means. ST (1-5 mg/kg) or PX (1-5 mg/kg) attenuated NC, with a similar inhibition found in both sexes (5 mg/kg, 180 min: ST - males: 124 ± 10 vs 714 ± 15 s in C; females: 116 ± 10 vs 718 ± 6 s in C; PX - males: 106 ± 10 vs 714 ± 14 s in C; females: 102 ± 10 vs 715 ± 14 s in C). At 0.3 mg/kg, neither of these drugs affected NC. Fluoxetine (1-25 mg/kg) also inhibited catalepsy, although the effect was not dose-dependent; no differences were observed between males and females (5 mg/kg, 180 min: males, 185 ± 14 vs 712 ± 14 s in C; females, 169 ± 10 vs 710 ± 19 s in C). For these SSRIs, maximal inhibition of NC was obtained with 5 mg/kg, 180 min after H. These results are consistent with the hypothesis that serotonergic mechanisms modulate nigrostriatal transmission, and suggest that SSRIs are possibly safe in depressive PD patients.

Effect of aspartate and glutamate on nociception, catalepsy and core temperature in rats.

Effects of excitatory aminoacids (EAAs) aspartate (ASP) and glutamate (GLU) in a low (50 ng, i.c.) and high dose (20 micrograms, i.c.), were studied on nociception, catalepsy and rectal temperature in albino rats. Both ASP and GLU altered the tail flick reaction time to thermal stimulation in a dose dependent manner, increasing it with low doses and reduced with high doses. Naloxone (10 micrograms, ic) antagonized the anti-nociceptive effect of EAAs while ketamine (10 micrograms, ic)-a NMDA receptor antagonist antagonized the hyperalgesic effect. These EAAs also antagonized catalepsy induced by haloperidol, chlorpromazine, trifluoperazine and morphine. Both ASP and GLU produced a hyperthermic response in all animals, including those in which hypothermia was induced by reserpine. These EAAs produced a comparable central modulatory effects on nociception, catalepsy and core temperature.

Effects of losartan on neuroleptic-induced catalepsy in mice

Neuroleptic-induced catalepsy remains a useful method to study central dopaminergic function in rodents. Evidence obtained in several studies indicates that this phenomenon can be modified by cholinergic, histaminergic and serotonergic manipulation. Angiotensin II is a central neurotransmitter acting through AT1 and AT2 receptors. There are few data on the effect of angiotensinergic drugs on dopaminergic transmission. We investigated the effect of losartan, a nonpeptide antagonist of central and peripheral AT1 receptors, on neuroleptic-induced catalepsy. Adult male albino mice, 26-35 g, were used. Catalepsy was induced with haloperidol (H; l mg/kg, ip) and measured at 30-min intervals by means of a bar test. Losartan (10 or 100 ng/kg) or saline (control; 0.13 ml) was injected intraperitoneally 20 min before H, with each animal (7 per group) being used only once. Losartan (10 and 100 ng/kg) significantly (P<0.05) potentiated the cataleptic effect of H in comparison to the control group (e.g. 264 ñ 26 and 299 ñ 68 sec, respectively, vs 89 ñ 24 sec for the control group, 90 min after H). No differences were demonstrable 120, 150 or 180 min after H. Considering the high selectivity and the pharmacokinetic properties of losartan, these data suggest that central angiotensin AT1 receptors play a role in neuroleptic-induced catalepsy. However, further studies are necessary to confirm this hypothesis and to clarify the mechanism(s) involved in this process.

Effects of the 5-HT receptor antagonists cyanopindolol, ICI 169,369, cisapride and granisetron on neuroleptic-induced catalepsy in mice

Typical neuroleptics (e.g. haloperidol) can induce catalepsy in rodents. Selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonists reduce neuroleptic-induced catalepsy (NIC), suggesting that this subtype of serotonin receptor plays a role in the modulation of nigrostriatal dopaminergic transmission. The present study was designed to evaluate the participation of other 5-HT receptor subtypes in NIC. Adult albino mice (both sexes, 26-35 g) were used. Catalepsy was induced with haloperidol (H; 1.5 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Cyanopindolol (a 5-HT1B receptor antagonist), ICI 169,369 (a 5-HT1C/2 receptor antagonist) and granisetron (a 5-HT3 receptor antagonist) were used. Buspirone, a 5-HT1A partial antagonist, cisapride, a 5-HT3/5-HT4 ligand and clomipramine, a 5-HT neuronal uptake blocker, were also employed. These drugs were injected ip, 20 min before H, with each animal (9-10 per group) used only once. Cyanopindolol (0.3 mg/kg) or ICI 169,369 (5 mg/kg) did not significantly affect NIC (375 +/- 39 and 378 +/- 34 s vs 372 +/- 44 s for controls, at 2 h after H). Buspirone (1 mg/kg) reduced, while pretreatments with either granisetron (0.5 mg/kg), cisapride (5 mg/kg) or clomipramine (5 mg/kg) potentiated the cataleptic effect of H (107 +/- 19, 576 +/- 52, 815 +/- 76 and 800 +/- 97 s vs 374 +/- 40 s in the control group, at 2 h after H).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of median raphe nucleus lesions on neuroleptic-induced catalepsy and on the anticataleptic effect of buspirone

Catalepsy induced by neuroleptics in rats can be modified by 5-hydroxytryptaminergic (5-HTergic) manipulation. For example, buspirone (BUS) and other central 5-HT1A receptor ligands reduce neuroleptic-induced catalepsy (NIC). The dorsal (DRN) and median (MRN) raphe nuclei are reported to be important sources of 5-HTergic projections to the basal ganglia, the site of action of neuroleptics in producing NIC. A previous study showed that lesion of DRN did not affect NIC or the anticataleptic effect of BUS. The present study was designed to evaluate the participation of MRN in NIC and in the anti-NIC effect of BUS. Twenty-four male Wistar rats (N = 6/group) weighing 220-250 g were used. Electrolytic lesion of MRN was carried out in anesthetized rats along with sham operations (electrode inserted but no current applied). Ten days later, the rats were injected with BUS (5 mg/kg, ip) or saline (1 ml, ip). Catalepsy was induced 20 min later with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. The Costall per cent Naylor method of scoring (range 0-5 points) was used. Saline-injected MRN-lesioned rats displayed significantly lower catalepsy scores than sham-lesioned rats (1.5 +/- 0.2 vs 3.8 +/- 0.3 at 90 min after H). In sham-lesioned rats, BUS significantly reduced the catalepsy scores in comparison with saline-treated animals (1.3 +/- 0.2 vs 3.8 +/- 0.3 at 90 min after H). However, BUS was not able to further reduce NIC in the MRN-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a single administration of buspirone on catalepsy, yawning and stereotypy in rats

In the present study, the effects of a single administration of buspirone (0.1, 0.3, 1.0, and 3.0 mg/kg sc-30 min before testing) on three dopamine-related behaviors were evaluated in 4-month old male Wistar rats (7-10 animals per group). Buspirone decreased haloperidol (2.0 mg/kg ip)-induced catalepsy in a dose-dependent manner (from 7.30 to 5.09 1n of s compared to the untreated control group). Apomorphine (0.06 mg/kg sc)-induced yawning was also dose-dependently reduced (from 26.7 to 0.9 yawns in 30 min) and so was apomorphine (1.0 mg/kg sc)-induced stereotypy (from 32.9 to 5.9, sum of scores). The present results indicate that buspirone presents unique pharmacological effects related to dopaminergic transmission not only in biochemical but also in behavioral terms

Dorsal raphe nucleus lesions have no effect on neuroleptic-induced catalepsy and on the anticataleptic activity of buspirone

The anxiolytic drug buspirone (BUS) and other central 5-HT-1A receptor ligands are capable of reducing neuroleptic-induced catalepsy in rodents. The dorsal raphe nucleus (DRN) is reported to be an important source of serotonergic projections to the basal ganglia, the site of neuroleptic action. The present study was designed to evaluate the participation of the DRN in the anticataleptic effect of BUS on male Wistar rats. Rats were submitted to electrolytic or sham DRN lesion under barbiturate anesthesia. Ten days later, the animals were injected with BUS (5 mg/kg,ip) or saline ( 1 ml, ip) and catalepsy was induced 20 min later with haloperidol (1 mg/kg, ip). Saline-injected DRN-lesioned and sham-lesioned rats displayed similar catalepsy score and BUS significantly and similarly reduced the catalepsy scores in both groups. The results suggest that, in producing anticataleptic effects, BUS interacts at sites other than the DRN. The participation of other raphe nuclei in the anticataleptic effect of BUS is currently under investigation