RESUMO
Stereotyped behavior can be induced by the dopamine agonist apomorphine or by the releasing agent amphetamine. Cholecystokinin influence on dopamine-mediated behaviors has been extensively studied but a real controversy remains. Our purpose was to further characterize the dopamine-cholecystokinin interaction in apomorphine- and amphetamine-induced stereotyped behavior using sulphated cholecystokinin octapeptide (CCK8) and cholecystokinin tetrapeptide (CCK4) treatments. The results showed that CCK8 decreases apomorphine-induced stereotyped behavior and CCK4 has no effect. CCK4 and CCK8 increased the amphetamine-induced stereotyped behavior; CCK4 was more effective. The results confirm the opposite modulation of apomorphine or amphetamine-induced stereotyped behavior by CCK. These data suggest that this modulation is mediated by both CCK receptors on apomorphine-induced and only by CCK(2) receptors on amphetamine-induced stereotyped behavior.
Assuntos
Anfetaminas/farmacologia , Apomorfina/farmacologia , Colecistocinina/farmacologia , Agonistas de Dopamina/farmacologia , Dopamina/metabolismo , Interações Medicamentosas , Animais , Masculino , Ratos , Ratos Wistar , Receptores da Colecistocinina/metabolismo , Sincalida/farmacologia , Sinapses/efeitos dos fármacos , Tetragastrina/farmacologia , Fatores de TempoRESUMO
Stereotyped behavior is elicited by activation of dopaminergic systems with drugs such as apomorphine and amphetamine. In previous studies, we have reported that the sulfated cholecystokinin octapeptide (CCK-8) decreased apomorphine-induced stereotypy in animals with normal and supersensitive dopamine receptors. The aim of the present study was to evaluate the effects of CCK(1) and CCK(2) receptor antagonists on stereotyped behavior induced by apomorphine or amphetamine. Rats were pretreated with the CCK(1) (SR 27897B; 1-[[2-(4-(2-chlorophenyl) thiazol-2-yl) aminocarbonyl]indolyl]acetic acid; 500 microg/kg; i.p.) or CCK(2) (L-365,260; 3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5 phenyl-1H-1, 4-benzodiazepine-3-yl)-N'-(3-methyl phenyl)-urea; 500 microg/kg; i.p. ) receptor antagonists or saline 15 min before apomorphine (0.6 mg/kg; s.c.) or amphetamine (9.0 mg/kg; i.p.) injection. Both CCK(1) and CCK(2) receptor antagonists significantly increased apomorphine-induced stereotypy. In contrast, only the blockade of CCK(2) receptors significantly decreased amphetamine-induced stereotypy. The results suggest a dual opposite mechanism for CCK-dopamine interactions. These data also suggest that both apomorphine- and amphetamine-induced stereotypy should be used whenever effects of drugs acting on dopaminergic systems are being assessed.
Assuntos
Anfetamina/farmacologia , Apomorfina/farmacologia , Receptores da Colecistocinina/antagonistas & inibidores , Comportamento Estereotipado/efeitos dos fármacos , Animais , Benzodiazepinonas/farmacologia , Dopamina/metabolismo , Ácidos Indolacéticos/farmacologia , Masculino , Compostos de Fenilureia/farmacologia , Ratos , Ratos Wistar , Receptor de Colecistocinina A , Receptor de Colecistocinina B , Receptores da Colecistocinina/fisiologia , Tiazóis/farmacologiaRESUMO
1. The goal was to verify if central or peripheral sulphated cholecystokinin octapeptide (CCK8) injections can modulate apomorphine (APO)-induced stereotyped behavior. Experiments were designed to determine the involvement of cholecystokinin receptor subtypes as well. 2. Animals which received CCK8 (0.0725, 0.145 and 14.5 nmol, icv) showed a significant (p < 0.05) decrease in APO (0.6 mg/kg, sc)-induced stereotyped behavior. 3. No other statistically significant difference was observed among groups. Since ip CCK8 (1.16 or 2.32 nmol/kg) injections did not interfere with APO-induced stereotypy, the results suggest that the CCK8 modulatory effects have a central action. 4. The results also suggest that the effects of icv CCK8 were not due to the stimulation of CCK8 receptors alone since central CCK4 (14.5 or 29.0 nmol) injections did not interfere with the expression of stereotypy.
Assuntos
Apomorfina/farmacologia , Sincalida/farmacologia , Comportamento Estereotipado/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos WistarRESUMO
Yawning behavior is an experimental tool to study physiological responses, to elucidate the mechanisms of action of some drugs and hormones, and it is also a paradigm for some diseases and for dopamine (DA) agonists' clinical use. In this study, the effects of 24- and 48-h fasting as well as the influence of the light-dark cycle on apomorphine (APO)-induced yawning were evaluated. Initially, control and 48-h-fasted adult male rats were tested for yawning induced by APO (50, 100, 150 micrograms/kg, SC). The most effective dose tested was 100 micrograms/kg. Fasting significantly lowered yawning in all doses tested. Comparison between 24- and 48-h-fasted rats for APO (100 micrograms/kg)-induced yawning showed no significant difference between groups. Ad lib-fed groups were tested for APO (100 micrograms/kg)-induced yawning in both the light and in the dark phases of the cycle. Total number of yawnings increased significantly in the dark period. The present data show that fasting reduces and dark period increases APO-induced yawning in rats, suggesting that these conditions modulate the expression of this behavior.
Assuntos
Apomorfina/farmacologia , Jejum/fisiologia , Bocejo/efeitos dos fármacos , Animais , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Wistar , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologia , Bocejo/fisiologiaRESUMO
Cholecystokinin (CCK-8) coexists with dopamine in some neurons and modulates dopaminergic neurotransmission. In the present study we determined the effect of CCK-8 on stereotyped behavior in supersensitive dopaminergic system. Adult male Wistar rats, weighing 200-250 g, were used. Dopaminergic supersensitivity was induced by long-term haloperidol (HAL) treatment (30 days: 1.0 mg/kg twice a day). Seventy-two hours after HAL withdrawal animals received CCK-8 (14.5 nmol/5 microliters) or saline intracerebroventricularly (icv) before being tested for apomorphine (APO, 0.6 mg/kg, sc)-induced stereotyped behavior. Experimental groups were: long-term HAL-treated rats that received saline (HSAL, N = 9) or CCK-8 (HCCK, N = 11) icv and long-term saline-treated rats that received CCK-8 (SCCK, N = 9) or saline (SSAL, N = 8) icv. As expected, HSAL rats showed statistically significant higher stereotypy scores than SSAL rats (42 +/- 1.7 vs 31 +/- 1.6; P < 0.05) and CCK-8 significantly reduced stereotyped behavior in supersensitive rats (42 +/- 1.7 vs 37 +/- 1.5; P < 0.05). These results show that CCK-8 icv reduces stereotypy in dopaminergic-supersensitive rats, and suggest that the dopamine supersensitivity phenomenon can be modulated by CCK-8.
Assuntos
Colecistocinina/administração & dosagem , Comportamento Estereotipado/efeitos dos fármacos , Análise de Variância , Animais , Apomorfina/farmacologia , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Haloperidol/farmacologia , Injeções Intraventriculares , Masculino , Ratos , Ratos Wistar , Sincalida/farmacologiaRESUMO
Cholecystokinin (CCK-8) coexists with dopamine in some neurons and modulates dopaminergic neurotransmission. In the present study we determined the effect of CCK-8 on stereotyped behavior in supersensitive dopaminergic system. Adult male Wistar rats, weighing 200-250 g, were used. Dopaminergic supersensitivity was induced by long-term haloperidol (HAL) treatment (30 days: 1.0 mg/kg twice a day). Seventy-two hours after HAL withdrawal animals received CCK-8 (14.5 nmol/5 µl) or saline intracerebroventricularly (icv) before being tested for apomorphine (APO, 0.6 mg/kg, sc)-induced stereotyped behavior. experimental groups were: long-term HAL-treated rats that received saline (HSAL, N = 9) or CCK-8 (HCCK, N = 11) icvand long-term saline-treated rats that received CCK-8(SCCK,N = 9) or saline (SSAL, N = 8) icv. As expected, HSAL rats showed statistically significant higher stereotypy scores than SSAL rats (42 + or - 1.7 vs 31 + or - 1.6; P<0.05) and CCK-8 icv reduces stereotypy in dopaminergic-supersensitive rats, and suggest that the dopamine supersensitivity phenomenon can be modulated by CCK-8