The role of D1 and D2 receptors in the heightened locomotion induced by direct and indirect dopamine agonists in rats with hippocampal damage: An animal analogue of schizophrenia

Effects of hippocampal damage on reward threshold and response rate during self-stimulation of the ventral tegmental area in the rat

“…First, maximal response rates for ICSS are usually considered to be a measure of motor performance [33]. Rats with hippocampal damage, produced by a variety of different methods, have been reported to display increased motor output in response to activating situations, food reward, and following drug administration [5,8,9,17,24,38,48,49,59,60]. These results may thus be another example of the enhancement in motor output resulting from hippocampal damage.…”

“…Although traditionally implicated in processes such as spatial memory [40,41], working memory [38], and response inhibition [1,18], accumulating evidence indicates that the hippocampal formation exerts an important modulatory influence over behaviors directly mediated by the nucleus accumbens (NACC). This modulatory influence has been consistently demonstrated in many studies of spontaneous and drug-induced locomotion.…”

“…Thus, it has been shown that extensive lesions of the hippocampal formation produce increases in spontaneous locomotion [9,24] and result in heightened locomotor responses to psychostimulants and dopamine agonists [5,38,47,59,60]. This enhancement in drug-induced activity following extensive hippocampal damage: (i) occurs as a direct function of increased locomotion and not indirectly, from reductions in competing behaviors [59]; (ii) is dependent on the integrity of the mesolimbic dopamine (DA) projection, as 6-OHDA lesions of the NACC block this effect [59]; (iii) occurs specifically in response to pharmacological stimulation of dopamine D2 receptors, which is consistent with the possibility of underlying receptorbased changes [38]; and (iv) corresponds to increases in amphetamine stimulated DA release in the NACC [60]. It is presumed that these changes occur as a function of the degeneration of hippocampal efferents innervating the NACC [4,17,19,20,27,50,51,55,56,63].…”

The Effects of Excitotoxic Hippocampal Lesions in Rats on Risperidone- and Olanzapine-Induced Locomotor Suppression

“…Locomotor activity was recorded for 30 min, and then animals were removed from the testing cage and received an injection of amphetamine. Following amphetamine injection, animals were immediately returned to the testing cages, and locomotor activity was recorded for an additional 60 min.Stereotypic grooming behavior (self-directed sniffing, licking, biting, or scratching with forelimbs or hindlimbs) was also assessed for 15 s every 20 min after amphetamine injection as a indirect measure of nigrostriatal dopamine function (Prosser et al 1989;Mittleman et al 1991Mittleman et al , 1993. Scores were rated as described in Bardgett et al (1997a): 0 -no grooming, 1 -grooming for less than 3 s, 2 -grooming for more than 3 s, 4 -continuous grooming.…”

Excitotoxic Lesions of the Rat Medial Prefrontal Cortex Effects on Abnormal Behaviors Associated with Neonatal Hippocampal Damage

“…Neonatal rats were lesioned in the mPFC. In adulthood, they showed attenuated locomotion in response to novelty, amphetamine, and Structural neurodevelopmental abnormalities in the temporolimbic cortex, dysfunction of the prefrontal cortex (PFC), and dysregulation of dopamine and glutamate systems are implicated in the pathophysiology of schizophrenia (Weinberger 1987;Robbins 1990;Grace 1991;Mittleman et al 1993;Weinberger and Lipska 1995). In an attempt to recreate these neuropathological features in an animal, we previously investigated the consequences of neonatal excitotoxic damage of the ventral hippocampal formation in the rat on behaviors related to dopamine and glutamate function (Lipska et al , 1995a Weinberger 1993, 1994; AlAmin et al 1997).…”