Neuroscience
-
κ opioid receptor agonists produce aversive effects in rodents, however the underlying mechanisms remain unclear. Activation of p38 mitogen-activated protein kinase (MAPK) has been discovered to play a critical role in the modulation of affective behaviors. ⋯ Stereotaxic microinjection of the p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridy-l)-1H-imidazole (SB203580) into amygdala significantly inhibited p38 MAPK activation and completely blocked the conditioned place aversion in mice. Thus, these results suggested that activation of p38 MAPK in the amygdala was required to mediate κ opioid receptor-induced aversive behavior.
-
The hypothalamus controls feeding behavior. Since central opioid systems may regulate feeding behavior, we examined the role of μ-, δ- and κ-opioid receptors in the lateral hypothalamus (LH), the hunger center, in feeding behavior of mice. Non-selective (naloxone; 3 mg/kg, s.c.) and selective μ- (β-funaltrexamine, β-FNA; 10 mg/kg, s.c.), δ- (naltrindole; 3 mg/kg, s.c.) and κ- (norbinaltorphimine, norBNI; 20 mg/kg, s.c.) opioid receptor antagonists significantly decreased food intake in food-deprived mice. ⋯ Naloxone (3mg/kg, s.c.) significantly increased the GABA level in the LH and both bicuculline and the GABA release inhibitor 3-mercaptopropionic acid (3-MP, 5 μg/side) attenuated the inhibitory effect of naloxone on feeding behavior. 3-MP also attenuated the effects of β-FNA and norBNI, but not that of naltrindole. These results show that opioid systems in the LH regulate feeding behavior through orexin neurons. Moreover, μ- and κ-, but not δ-, opioid receptor antagonists inhibit feeding behavior by activating GABA neurons in the LH.
-
Studies on classification learning suggested that altered dopamine function in Parkinson's Disease (PD) specifically affects learning from feedback. In patients OFF medication, enhanced learning from negative feedback has been described. This learning bias was not seen in observational learning from feedback, indicating different neural mechanisms for this type of learning. ⋯ Also, patients and controls showed comparable evidence of feedback processing in observational learning. In active feedback learning, PD patients use alternative learning strategies than healthy controls. Analyses on observational learning did not yield differences between patients and controls, adding to recent evidence of a differential role of the human striatum in active and observational learning from feedback.
-
Animals change their biological activities depending on their nutritional state. Reproductive functions, including sexual behavior, are suppressed under low-energy conditions; however, the underlying neuronal mechanism is poorly understood. Neuropeptide Y (NPY) is an orexigenic molecule released in response to low-energy conditions and has an inhibitory effect on sexual behavior. ⋯ Direct injection of NPY or 8-OH-DPAT (a 5-HT1A receptor agonist that inhibits the activity of 5-HT neurons) into the DRN inhibited male sexual behavior in fed males. In contrast, injection of BIBP-3226, a NPY Y1 receptor antagonist, or (+)-DOI hydrochloride (DOI), a 5-HT2A/2C receptor agonist that activates 5-HT neurons, into the DRN partially recovered male sexual behavior in 24-h fasted males. These results suggest that NPY inhibits serotonergic neuronal activity via the Y1 receptor in the DRN, resulting in suppression of male sexual behavior in low-energy conditions.
-
Rewarding memories induced by addictive drugs may contribute to persistent drug-seeking behaviors, which is an important contributing factor to drug addiction. However, the biological mechanisms underlying drug-associated rewarding memories have not yet been fully understood, especially the new synthetic drugs, such as amphetamine-type stimulants (ATS). ⋯ Thus, this study extends previous findings by showing that GABAA receptors, particularly the α1-containing GABAA receptors, may be strongly implicated in METH-associated rewarding memories. This work provides us with a new perspective on the goal of treating ATS addiction.