Glucocorticoids attenuate haloperidol-induced catalepsy through adrenal catecholamines

Abstract

To examine the influence of adrenal secretions on neuroleptic induced catalepsy, we studied the effect of adrenocorticoids, noradrenaline (NA) or adrenaline (AD) on haloperidol (HAL) induced catalepsy in adrenalectomised (ADX) and sham-adrenalectomised (sham-ADX) rats. HAL (1 mg/kg, i.p.) induced a greater degree of catalepsy in ADX rats as compared to sham-ADX rats. Corticosterone (CORT, 1-2 mg/kg, s.c.) or dexamethasone (1-2 mg/kg, s.c.) attenuated the HAL catalepsy in sham-ADX but not in ADX rats. Further, when the HAL (1 mg/kg) catalepsy score was maximal (at 120 min), the rats were subjected to cold stress (3 degrees C for 10 min) or treated with NA, AD (2 micrograms/kg, i.v.) or CORT (2 mg/kg, s.c.). After cold stress procedure or CORT treatment, the catalepsy was significantly reduced in sham-ADX but not in ADX rats, whereas NA or AD infusion caused an immediate but short lasting significant decrease in HAL catalepsy in both sham-ADX and ADX rats. The anticataleptic effect of NA or glucocorticoids was blocked by an alpha 1 adrenoceptor blocker, prazosin. These findings suggest that peripheral noradrenergic and adrenergic mechanisms play an important role in the neuroleptic induced catalepsy. Such mechanisms may mediate the anticataleptic action of glucocorticoids.

Emerging Evidence for a Central Epinephrine-Innervated α1-Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression

“…This agrees with the finding that EPI has the highest efficacy of all tested catecholamines at a 1 -receptors coupled to phosphatidylinositol hydrolysis or potentiation of cAMP responses in rat brain slices (Johnson and Minneman, 1986). Furthermore, pharmacological inhibition of PNMT, which causes a depletion of extracellular EPI but not of NE (Routledge and Marsden, 1987a), has been found to produce marked behavioral inactivity and to abolish appetitive hypothalamic self-stimulation in rats and mice , while stressors that release EPI, peripheral administration of EPI (Chopde et al, 1995;Yntema and Korf, 1987), and glucocorticoids that induce PNMT (Chopde et al, 1995) have all been found to reverse the catalepsy induced by neuroleptics probably via a 1 -receptor stimulation. Ivt.…”

Haloperidol Administration in Humans Lowers Plasma Nerve Growth Factor Level: Evidence that Sedation Induces Opposite Effects to Arousal

“…Furthermore, since NGF is implicated in growth, differentiation, and other metabolic activities in cells of the nervous, endocrine and immune systems [4], it may also be possible that the seda tion status, like the cataleptic status in animals induced by HA treatment, might impair one or more of these NGFcontrolled functions. In line with this hypothesis is the fact that HA alters calcium channel fluxes [14], and Nmethyl-rZ-aspartate (NMDA) receptors [21], two events which can influence NGF synthesis and release [12,22,23].…”

“…In order to investigate this aspect, we studied the effect of haloperidol (HA) used clinically in psychotic patients inducing sedation and catalepsy [11][12][13][14] on basal NGF plasma levels. In a previous study, we reported that the injection of HA in adult mice lowers brain NGF levels and that the effect is time-and dose-dependent.…”

Early Life Stress Causes Refractoriness to Haloperidol-Induced Catalepsy

“…In rats, single exposure to a low-intensity stressor enhances haloperidolinduced catalepsy after 2 weeks, whereas exposure to a highintensity stressor produces opposite effects (Antelman et al, 1991(Antelman et al, , 1992. Acute treatment with glucocorticoids attenuates haloperidol-induced catalepsy via a peripheral mechanism mediated by the release of catecholamines from adrenal medulla (Chopde et al, 1995). Whether early-life stress influences the vulnerability to antipsychotic-induced EPS in adult life is unknown.…”

“…Chopde et al (1995) have found that glucocorticoids restrain haloperidol-induced catalepsy in rats by enhancing catecholamine release from the adrenal medulla. Hence, we measured norepinephrine and epinephrine levels in control and PRS rats 1 hour after injection of saline or 2 mg/kg of haloperidol.…”