Chronic administration of haloperidol during development: Behavioral and psychopharmacological effects

Abstract

Chronic haloperidol treatment during prenatal and postnatal development was found to induce long-term behavioral and psychopharmacological effects. Rats tested shortly after termination of the chronic treatment at weaning or as young adults were hyperactive in the open field and exhibited an attenuated behavioral response to amphetamine and an accentuated cataleptic response to later doses of haloperidol, when compared with control offspring of the same age. Tests at an intermediate interval (adolescence period) showed no significant difference from control offspring on any of these behavioral measures. Adult rats administered haloperidol chronically for the same duration were also hyperactive after termination of treatment. In contrast to the effects of haloperidol during development, these adults exhibited an accentuated behavioral response to amphetamine and an attenuated cataleptic response to a later dose of haloperidol. Compensatory mechanisms in response to chronic haloperidol treatment during development thus appear to be different from those in adulthood.

Olanzapine Sensitization and Clozapine Tolerance: From Adolescence to Adulthood in the Conditioned Avoidance Response Model

“…Indeed, very little prior research has been done on this topic. We could only find one study that showed a haloperidol-induced sensitization effect on catalepsy (Spear et al, 1980). The lack of research on this topic is not surprising given that antipsychotic sensitization and tolerance are relatively newly recognized phenomena even in adult animals Zhang and Li, 2012).…”

The adolescent brain and age-related behavioral manifestations

“…Ref. [513]). They also frequently appear hyper-reactive to stimuli, displaying substantially greater startle response amplitude than adults (S. Brasser, personal communication).…”

Steps to a neurochemistry of personality

“…The notion that early experience has prolonged effects on VTA DA functional properties is supported by findings that uncontrollable prenatal stress produced permanent alterations in NAS and prefrontal DA transmission in adulthood (Deminiere et al 1992;Fride & Weinstock 1988). Similarly, persistent changes in DA metabolism and behavior have been observed with the administration of psychostimulants during periods of rapid developmental change (Feigenbaum & Yanai 1984;Middaugh & Zemp 1985;Spear & Brake 1983;Spear et al 1980).…”

“…Therefore, the outcomes of such periods might establish different trajectories in the functional development of the VTA DA system across individuals, and thus partially specify eventual trait levels of behavioral facilitation. It is unknown whether experienceexpectant processes are a significant source of individual differences in DA transmission, although the effects of drug-induced DA activation on behavior during periods of rapid developmental change can be persistent (Feigenbaum & Yanai 1984;Middaugh & Zemp 1985;Spear & Brake 1983;Spear et al 1980). An initial task is to identify sensitive periods in the postnatal development of the VTA DA system -for example, as marked behaviorally around 1 year of age in humans by a relatively abrupt increase in locomotor exploration of novel environments.…”

“…The notion that early experience has prolonged effects on VTA DA functional properties is supported by findings that uncontrollable prenatal stress produced permanent alterations in NAS and prefrontal DA transmission in adulthood (Deminiere et al 1992;Fride & Weinstock 1988). Similarly, persistent changes in DA metabolism and behavior have been observed with the administration of psychostimulants during periods of rapid developmental change (Feigenbaum & Yanai 1984;Middaugh & Zemp 1985;Spear & Brake 1983;Spear et al 1980).Thus, early experiential processes may lay the foundation for trends in positive incentive motivated behavior by moderating the strength of later experience-dependent processes involving the functional capacities of the VTA DA projection system (Collins & Depue 1992). For example, stable individual differences in VTA DA transmission appear to affect the expression of behavioral sensitization by modifying the strength of synaptic connections of contextual efferents in the NAS.…”