Stereotyped behavior elicited by amphetamine in the rat: Influences of the testes

Beatty, William W.; Dodge, Anthony M.; Traylor, Kathy L.

doi:10.1016/0091-3057(82)90416-6

Cited by 46 publications

(35 citation statements)

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“…Thus, the low specificity of FIN and other 5AR inhibitors for 5AR isozymes in rats (Thigpen and Russell, 1992) and our lack of data on the brain regional levels of NSs following 5AR blockade currently limit the identification of the molecular bases of the antipsychotic-like properties of these compounds. Nevertheless, our findings support previous functional and anatomical evidence on the modulatory role of NSs on striatal and cortical dopaminergic functions (Beatty et al, 1982;Bitar et al, 1991;Dluzen et al, 1986;Engel et al, 1979;Fabre-Nys, 1998;Hernandez et al, 1994;Menniti and Baum, 1981;Savageau and Beatty, 1981). NSs have been shown to affect the extracellular levels of dopamine in prefrontal cortex and striatum (Cabrera et al, 2002;Petitclerc et al, 1995).…”

Section: -A-reductase Inhibitors In Models Of Psychosis M Bortolato supporting

confidence: 81%

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Bortolato

Frau

Orrù

et al. 2008

Neuropsychopharmacol

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Recent evidence indicates that neuroactive steroids may participate in the pathogenesis of schizophrenia spectrum disorders, yet the mechanisms of this involvement are elusive. As 5-a-reductase (5AR) is the rate-limiting enzyme of one of the two major metabolic pathways in brain steroidogenesis, we investigated the effects of its blockade in several rat models of psychotic-like behavior. The 5AR inhibitor finasteride (FIN, 60 or 100 mg/kg, intraperitoneal, i.p.) dose-and time-dependently antagonized prepulse inhibition (PPI) deficits induced by apomorphine (APO, 0.25 mg/kg, subcutaneous, s.c.) and d-amphetamine (AMPH, 5 mg/kg, s.c.), in a manner analogous to haloperidol (HAL, 0.1 mg/kg, i.p.) and clozapine (CLO, 5 mg/kg, i.p.). Similar results were observed with the other 5AR inhibitors dutasteride (DUT, 40 or 80 mg/kg, i.p.) and SKF 105111 (30 mg/kg, i.p.). FIN (60 or 100 mg/kg, i.p.) also reduced hyperlocomotion induced by AMPH (1 or 3 mg/kg, s.c.) and attenuated stereotyped behaviors induced by APO (0.25 mg/kg, s.c.). Nevertheless, FIN (100 mg/kg, i.p.) did not reverse the PPI disruption induced by the N-methyl-d-aspartate receptor antagonist dizocilpine (0.1 mg/kg, s.c.). FIN (60-300 mg/kg, i.p.) induced no catalepsy in either the bar test or the paw test. Our results suggest that 5AR inhibitors elicit antipsychotic-like effects in animals and may be proposed as a putative novel target in the management of psychotic disorders.

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Section: -A-reductase Inhibitors In Models Of Psychosis M Bortolato supporting

confidence: 81%

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Bortolato

Frau

Orrù

et al. 2008

Neuropsychopharmacol

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“…Similar to the present results, Dluzen et al (1986) found that castration increased amphetamine-stimulated rearing behavior. Adult castration increased the duration of stereotyped behavior in response to injection of 5 mg/kg amphetamine (Beatty et al 1982). This same study found that exogenous testosterone decreased stereotypy in castrated males and ovariectomized females.…”

Section: Discussionsupporting

confidence: 62%

“…Orchidectomy effects on behavioral responses to stimulants are even less understood. Camp and Robinson (1988b) and Beatty et al (1982) reported that castration increased amphetamine-induced stereotypy but not locomotion.A consistent picture about the role of gonadal steroids on behavioral responses to stimulants has been elusive. Different behavioral strategies and paradigms used by different authors and the absence of males in many studies have complicated the issue.…”

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confidence: 99%

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Sex Differences in Cocaine-Stimulated Motor Behavior Disparate Effects of Gonadectomy

Walker

Cabassa

Kaplan

et al. 2001

Neuropsychopharmacology

112

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Sex differences in biological substrates of drug use and addiction are poorly understood. The present study investigated sexual dimorphisms in motor behavior following acute cocaine administration (10, 20, or 40 mg/ kg, i.p Little is known about sex differences in biologic substrates of drug taking and addiction. However, an emerging literature documents that sex differences in the behavioral responses to addictive drugs exist in humans. A sex difference in human affective responses to cocaine has been reported in one study in which females reported more nervousness than males following intranasal cocaine (Kosten et al. 1996). Lukas and coworkers (1996) showed that cocaine induced similar cardiovascular and affective responses in men and women, although plasma concentrations of cocaine were lower in women. In a laboratory setting, cocaine cues induced more drug craving in female than male addicts (Robbins et al. 1999). These results suggest that women may be more sensitive to cocaine than men. In fact, women begin using cocaine and enter treatment at earlier ages than men (Griffin et al. 1989;Mendelson et al. 1991) and have more severe cocaine use at intake than men (Kosten et al. 1993). .). Cocaine increased stereotypy rating, horizontal and vertical activity in both sexes, and effects were always greater in females than males. A population analysis using data from multiple experiments indicated that horizontal activity scores were normally distributed in males butSex differences in spontaneous and drug-stimulated behavior have been carefully studied in animals. Probably the most robust sex difference in behavior is the observation that female rats exhibit more running wheel activity than males (for review see Beatty 1979). Female rats are also often reported to be more active than males in open-field situations (Beatty 1979). These sex differences in basal or non-stimulated behavior are likely related to the reported sex differences in open-field behavior following psychomotor stimulant administration (van Hartesveldt and Joyce 1986 25 , NO . 1 Sex Differences in Cocaine Effects 119 particularly well known for producing greater behavioral effects in female rats following acute administration (Schneider and Norton 1979;Savageau and Beatty 1981;Becker et al. 1982;Camp et al. 1986;Camp and Robinson 1988a). Acute cocaine administration has also been reported to induce greater behavioral effects in female rats (van Haaren and Meyer 1991;Haney et al. 1994;Bowman and Kuhn 1996) and in mice (Sershen et al. 1998). However, in other reports, sex differences in acute cocaine-stimulated motor behavior were not observed in naïve Sprague-Dawley rats (Craft and Stratman 1996) and in three other rat strains (Cailhol and Mormede 1999). Thus, better evidence of sex-differences in acute behavioral effects in intact animals exists for amphetamine than cocaine. Gonadal and especially ovarian hormones have been investigated as likely modulators of these sex differences in behavior. Ovarian hormone effects on stimulant respon...

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“…The role of the male gonadal steroid hormone, testosterone, upon the nigro-striatal dopaminergic system has received relatively less attention. Indirect indices of dopaminergic activity as determined with amphetamine-stimulated behavioral measures have indicated that testosterone attenuates the effects of amphetamine on locomotor activity and stereotyped behavior (7)(8)(9) and the duration of specific amphetamine-stimulated behaviors in castrated male rats are prolonged compared to those of intact and castrated plus testosterone-treated male rats (10). In addition, castration reduces and testosterone reinstates yawning behavior in male rats (1 l), a behavior, which in part, appears to be under control of the dopaminergic system (12).…”

mentioning

confidence: 99%

Effects of Orchidectomy on Nigro‐Striatal Dopaminergic Function: Behavioral and Physiological Evidence

Dluzen

Ramírez

1989

J Neuroendocrinology

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In the present experiments, we examined the effect of castration upon two indices of nigro-striatal dopaminergic function in the male rat. In Experiment I, differences in spontaneous locomotor behavioral activity between intact and castrated male rats were examined. The total distance traveled, horizontal activity and mean revolutions of castrated male rats were significantly greater than that of intact males. No significant differences between intact and castrated males were obtained for vertical activity. In Experiment 11, the spontaneous in vifrodopamine release from the corpus striatum of intact and castrated rats as sampled during the light-phase (1500 h) and dark-phase (2400 h) of the photoperiod was examined. At both time periods, the spontaneous in vifrodopamine release of castrated males was significantly greater than that of intact males. Both intact and castrated males showed statistically significant increases in dopamine release at the 2400 h compared to the 1500 h time period. To examine if testicular hormones were responsible for these castration induced changes in dopamine release, in Experiment Ill we treated castrated male rats with testosterone propionate. Administration of testosterone propionate (0.1 mg/day x 5 days) significantly reduced in vifro dopamine release compared to untreated or castrated male rats receiving vehicle treatment. These results demonstrate that testicular hormones, most likely testosterone, have a markedly suppressive effect upon the nigro-striatal dopaminergic system as evidenced from changes in spontaneous behavioral activity and in vifro dopamine release.Within our laboratory, we have been interested in examining the modulatory effects of gonadal steroid hormones upon the nigrostriatal dopaminergic system of the female rat (1, 2). Our results, as well as those from other laboratories, have demonstrated that the corpus striatum (CS) is an important target site of the CNS for both estrogen and progesterone (3-6). The role of the male gonadal steroid hormone, testosterone, upon the nigro-striatal dopaminergic system has received relatively less attention. Indirect indices of dopaminergic activity as determined with amphetamine-stimulated behavioral measures have indicated that testosterone attenuates the effects of amphetamine on locomotor activity and stereotyped behavior (7-9) and the duration of specific amphetamine-stimulated behaviors in castrated male rats are prolonged compared to those of intact and castrated plus testosterone-treated male rats (10). In addition, castration reduces and testosterone reinstates yawning behavior in male rats (1 l), a behavior, which in part, appears to be under control of the dopaminergic system (12). These results suggest that, similar to that of the female, the nigro-striatal dopaminergic system of the male rat is also subject to the influences of gonadal steroids. More specifically, it would appear that testicular steroids exert a predominantly suppressive effect upon dopaminergic activity in the male rat.In this report...

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Stereotyped behavior elicited by amphetamine in the rat: Influences of the testes

Cited by 46 publications

References 18 publications

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Antipsychotic-Like Properties of 5-α-Reductase Inhibitors

Sex Differences in Cocaine-Stimulated Motor Behavior Disparate Effects of Gonadectomy

Effects of Orchidectomy on Nigro‐Striatal Dopaminergic Function: Behavioral and Physiological Evidence

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