ABSTRACT
A synergistic relationship is thought to exist between hypothalamic-pituitary-adrenal (HPA) axis activity and dopamine neurotransmission. To test whether a high response to dopamine indeed implies a hyperactive HPA-axis, we here used Wistar rats that were selected twice independently (original and replicate lines) for a high or low susceptibility to the dopamine receptor agonist apomorphine (so-called APO-SUS and APO-UNSUS rats, respectively). The APO-SUS rats from the original line displayed a hyperactive HPA-axis in that higher basal and stress-induced adrenocorticotropic hormone (ACTH) levels, and lower basal free-corticosterone levels were observed than those found in the original APO-UNSUS rats. In contrast, the activity of the HPA-axis in the APO-SUS rats from the replicate line did not differ from that in the replicate APO-UNSUS rats. Thus, in the APO-SUS/APO-UNSUS rat model the level of HPA-axis activity is not necessarily causally linked to dopamine responsiveness, implying that a hyperactive HPA-axis is not a prerequisite for a high dopaminergic response.
Subject(s)
Apomorphine/pharmacology , Behavior, Animal/drug effects , Dopamine Agonists/pharmacology , Dopamine/metabolism , Hypothalamo-Hypophyseal System/physiology , Pituitary-Adrenal System/physiology , Adrenocorticotropic Hormone/metabolism , Analysis of Variance , Animals , Corticosterone/metabolism , Exploratory Behavior/drug effects , Male , Polymorphism, Single Nucleotide/genetics , Rats , Rats, Wistar , Transcortin/geneticsABSTRACT
Although it has long been realized that the hippocampal formation receives a projection from the midbrain dopaminergic cell groups and contains mRNA for all five dopamine receptors, the functional role of this dopaminergic projection has not been studied so far. The present study aimed to investigate the role of dopamine receptors in the dorsal CA1 area of the hippocampus in prepulse inhibition. The results show that local application of amphetamine reduced prepulse inhibition without affecting the baseline startle amplitude. This effect of amphetamine could be reversed by coadministration of the D1 antagonist SCH23390. Moreover, local application of the D1 agonist SKF81297 also disrupted prepulse inhibition without altering basal startle amplitude. These data clearly suggest that the hippocampal D1 receptor plays an important role in prepulse inhibition. The effects of amphetamine could not be reversed by coadministration of the D2 antagonist sulpiride. Interestingly, the D2/3 agonist quinpirole did reduce prepulse inhibition, again without affecting basal startle amplitude. Because quinpirole has a much higher affinity for the D3 receptor than does sulpiride, it is suggested that the D3 receptor might be involved in this effect.
