Behavioural brain research
-
Comparative Study
Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice.
The still unknown contribution of the D4 receptors to memory consolidation was studied examining the memory effects of the dopamine D4 agonist PD168,077, the putative dopamine D4 antagonist L745,870, their mutual combination, and the combination of the D4 agonist with representative compounds acting as agonist or antagonist on the D1, D2 and the D3 receptors. Memory consolidation was assessed in C57BL/6J mice using the one-trial step-through inhibitory avoidance task, the compounds being injected immediately after training (foot-shock) and performance measured 24h later. PD168,077 (0.5-10mg/kg) dose-dependently improved memory performance and L745,870 (0.05-5mg/kg) at doses lower than 1mg/kg increased and at doses higher than 1mg/kg impaired memory performance. ⋯ The dopamine D3 antagonist U99194A (2.5-10mg/kg) did not affect the promnesic effects induced by the D4 agonist, which nevertheless abolished the U99194A-induced promnesic effects. Additionally, the amnesic effects produced by the D3 agonist 7-OH-DPAT (0.01-1 microg/kg) was attenuated by PD168,077. These results suggest a potential role of dopamine D4 receptors in memory consolidation, which would be similar to that of the D1 and D2 receptors and probably opposite to that of the D3 receptors.
-
Animals made ill by intraperitoneal injection with toxins, such as lithium chloride (LiCl) or lipopolysaccharides (LPS), or presented with cues associated with LiCl become hyperalgesic [Pain 56 (1994) 227]. The descending pronociceptive neurocircuitry and spinal pharmacology that underlie these effects bear the same features as those that mediate analgesic tolerance to morphine [Neurosci. Biobehav. ⋯ Furthermore, these effects occurred in the absence of detectable hyperalgesia indicating that illness-induced tolerance was not the result of an increase in pain sensitivity offsetting analgesia. Finally, rats tested in a context associated with LiCl demonstrated less morphine analgesia than rats tested in a context not associated with LiCl or rats naive to LiCl suggesting that illness activates descending mechanisms that antagonize analgesia rather than simply desensitizing opioid receptors. Thus, in addition to provoking hyperalgesia, illness-inducing agents also activate endogenous antianalgesic mechanisms.