Interactions between D-ala-met-enkephalin, A10 dopaminergic neurones, and spontaneous behaviour in the rat.
We have investigated the interaction between opioid peptides and dopaminergic A10 (DA-A10) neurones in the ventral tegmental area (VTA). The behavioural consequences of VTA infusion of d-Ala-Met-enkephalinamide (DALA) were analyzed. DALA elicited a dose-dependent increase in locomotor activity measured in photocell cages and the circular corridor. Observations in the open field and in a hole box revealed that DALA-induced behavioural stimulation was characterized by enhancement of locomotion, rearing, and number of hole visits, while grooming time and duration of hole visits were decreased. DALA-induced stimulation was reserved by naloxone, and was completely blocked by 6-OHDA destruction of DA-A10 terminals. d-Amphetamine-induced behavioural activation was potentiated by simultaneous VTA infusion of DALA which indicates that the behavioural response to DALA is dependent on DA-A10 neuronal activity. It is postulated that stimulation of opiate receptors exerts a presynaptic inhibition of an inhibitory input to DA-A10 neurones (eg. GABA or dendritic DA), thus releasing dopaminergic activity. In contrast to the acute effect, the d-amphetamine response was strongly attenuated 4 h, 1 and 6 days after VTA infusion of DALA, and returned to normal only at 14 days. This long-lasting modification may reflect decreased activity of opioid neurones, releasing the inhibition of DA-A10 neurones. Our findings suggest that endogenous opioid peptides may exert a modulatory influence on the dopaminergic mesocorticolimbic system.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives*; D004745:Enkephalins / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology*
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D004744:Enkephalin, Methionine; C013801:enkephalin-Met, Ala(2)-; D003913:Dextroamphetamine; D004298:Dopamine