Behavioral and biochemical studies of dopamine receptor sensitivity in differentially housed mice

Abstract

Group housed and individually housed mice were compared in (1) the motor activity responses to direct and indirect dopamine (DA) agonists, (2) in vivo presynaptic autoreceptor sensitivity and (3) in vitro binding of 3H-spiperone. Relative to group housed mice, individually housed mice showed an increased motor activity response to amphetamine, 1.25 and 0.625 mg/kg. Using two in vivo measures of presynaptic DA receptor sensitivity, the antagonism of spontaneous locomotor activity and the antagonism of dihydroxyphenylalanine (DOPA) accumulation by apomorphine (APO), individually housed mice showed greater activity counts and higher DOPA accumulations than group housed mice. Levels of tyrosine were significantly greater in individually housed mice. Significant effects of housing were also noted with the motor activity response to APO, 0.075-0.300 mg/kg, following pretreatment with reserpine, an in vivo measure of postsynaptic receptor sensitivity. However, there was no effect of housing on the number or affinity of 3H-spiperone binding sites in the striatum. These results are discussed in terms of the presynaptic activity of catecholaminergic neurons and the postsynaptic receptor sensitivity to APO in individually housed mice.

The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex

“…Second, we observed a clear potentiation of the amphetamine hyperlocomotor response in male mice that is in agreement with previous mouse studies (Wilmot et al 1984(Wilmot et al , 1986. These findings in mice contrasted with the failure to obtain such an effect in Sprague-Dawley rats by Weiss et al (2001a).…”

“…These findings are indicative of mesolimbic hyperdopaminergia (Dai et al 2004;Heidbreder et al 2000;Jones et al 1990;Leng et al 2004;Wilmot et al 1986), which is closely related to the genesis of positive symptoms in schizophrenia (e.g., Gray et al 1991;Laruelle et al 1999). …”

“…The more robust effects of the isolation syndrome are: (1) increased spontaneous locomotor activity which often expresses in the form of habituation deficit (mice: Abramov et al 2004;Benton and Brain 1981;rats: Domeney and Feldon 1998;Gentsch et al 1988;Heidbreder et al 2000), with few exceptions limited to specific strains (Geyer et al 1993;Weiss et al 2000Weiss et al , 2001a; and (2) enhancement of the sensitivity to amphetamine (mice: Wilmot et al 1984Wilmot et al , 1986and rats: Jones et al 1990;Sahakian et al 1975;Smith et al 1997;Weiss et al 2001a). These findings are indicative of mesolimbic hyperdopaminergia (Dai et al 2004;Heidbreder et al 2000;Jones et al 1990;Leng et al 2004;Wilmot et al 1986), which is closely related to the genesis of positive symptoms in schizophrenia (e.g., Gray et al 1991;Laruelle et al 1999).…”

Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders

“…In our stress model, concentrations of plasma corticosterone in isolated mice were significantly increased compared to control levels. Social isolation stress, caused by abolished social interaction among animals, has been reported to induce behavioural changes as a result of elevated levels of circulating corticosterone (Stranahan et al 2006) in rats and mice ; increased locomotor activity in a novel environment (Guo et al 2004 ;Lapiz et al 2003 ;Wilmot et al 1986), increased anxiety in an elevated plus-maze (Molina-Hernandez et al 2001), increased depressive-like behaviour in the forced swimming test (Brenes & Fornaguera, 2008), and impaired learning and memory in the one-trial passive avoidance test (Chida et al 2006). Further, social isolation for 6 h/d during PD 15-21 was sufficient to cause an acute elevation of corticosterone levels, leading to an impairment of performance in the Morris water maze task when animals were tested on PD 22-24 (Frisone et al 2002).…”

Social Deprivation, Social–Emotional Behavior, and the Plasticity of Dopamine Function

“…There are pharmacological and neurochemical studies supporting this hypothesis. Compared to animals that had been reared in social groups, isolated animals have been generally characterized by enhanced sensitivity to the stimulant effects of d-amphetamine, apomorphine, or cocaine (Ahmed, Stinus, Le Moal, & Cador, 1995;Jones et al, 1990;Lewis et al, 1990;Phillips et al, 1994;Wilmot, Vanderwende, & Spoerlein, 1986). Although some studies did not report this effect (Bowling & Bardo, 1994;Hall, Fong, Ghaed, & Pert, 2001;Jones, Hernandez, Kendall, Marsden, & Robbins, 1992;Weiss, Domeney, Heidbreder, Moreau, & Feldon, 2001), these observations Paul L. Gendreau and Mark H. Lewis suggest that social deprivation heightens social-emotional reactivity by means of alterations in DA sensitivity.…”