Long-term effects of early social isolation in Macaca mulatta: changes in dopamine receptor function following apomorphine challenge

Abstract

The hypothesis that early social isolation results in long-term alterations in dopamine receptor sensitivity was tested using older adult rhesus monkeys. Isolated and control monkeys were challenged with apomorphine (0.1 and 0.3 mg/kg), and the drug effects on spontaneous blink rate, stereotyped behavior, and self-injurious behavior were quantified using observational measures. Monoamine metabolites were quantified from cisternal CSF by HPLC-EC, prior to pharmacological challenge. Isolated and control monkeys did not differ in CSF concentrations of HVA, 5-HIAA, or MHPG. At the higher dose, apomorphine significantly increased the rate of blinking, the occurrence of whole-body stereotypies, and the intensity of stereotyped behavior (as measured by observer ratings) in isolated monkeys. The frequency of occurrence of self-injurious behavior was too low to allow for meaningful comparisons. These significant differences in response to apomorphine challenge support the hypothesis that long-term or permanent alterations in dopamine receptor sensitivity, as assessed by drug challenge, are a consequence of early social deprivation.

Evidence for a relationship between cage stereotypies and behavioural disinhibition in laboratory rodents

“…[32]). Similarly, isolation-rearing induces both stereotypy and changes in basal ganglia dopaminergic tone [36,37,42], as does premature weaning [24,63]. Basal ganglia lesions in humans are similarly associated with stereotypy-like behaviour [1,39].…”

Central Nervous System Monoamine Correlates of Social Dominance in Cynomolgus Monkeys (Macaca fascicularis)

“…Work by numerous investigators suggests that, in monkeys, monoamine metabolite concentrations in CSF are stable over time and across environments; furthermore, CSF concentrations observed in young animals are often predictive of those observed in the same individuals later in life. (Lewis et al 1990;Higley et al 1991Higley et al , 1996bRaleigh et al 1992). In the current study, animals were housed in unisexual groups of five or six animals (five groups of males, four groups of females) that were initially composed of social strangers, but which had been allowed to stabilize for at least one year prior to CSF collection.…”

Social Isolation in the Rat Produces Developmentally Specific Deficits in Prepulse Inhibition of the Acoustic Startle Response Without Disrupting Latent Inhibition

“…Variations in early social experience have been shown to have profound effects on the adult behavior, brain morphology, and neurochemistry of a variety of spe cies (Sachser 1986;Lewis et al 1990;Martin et al 1991;Jones et al 1992). For example, rearing rats in social iso lation from the weaning age produces behavioral ab normalities that include increases in spontaneous and response that were specific to isolation-reared animals.…”

“…Both isolation-reared animals (those isolated from the weaning age) and isolation-housed animals (those isolated as adults) were hyperactive when placed in a novel environment. Social isolation also led to deficits in PPI of the acoustic startle KEY WORDS: Social isolation; Locomotor activity; Prepulse inhibition; Latent inhibition; Dopamine; Ventral striatumVariations in early social experience have been shown to have profound effects on the adult behavior, brain morphology, and neurochemistry of a variety of spe cies (Sachser 1986;Lewis et al 1990;Martin et al 1991;Jones et al 1992). For example, rearing rats in social iso lation from the weaning age produces behavioral ab normalities that include increases in spontaneous and response that were specific to isolation-reared animals.…”