Presynaptic alpha-adrenergic mediation of self-stimulation in locus coeruleus in rats treated neonatally with 6-hydroxydopamine.
Rats self-stimulating in the region of the locus coeruleus and treated neonatally with 6-hydroxydopamine (6-OHDA) injected bilaterally in the same region were tested for effects of adrenergic receptor blockers on a lever-pressing behavior to obtain the brain reward. The neonatally treated animals (16 microgram total dose, 8 microgram X 2) self-stimulated at abnormally high rates compared with controls. Yohimbine (5 mg/kg i.p.) and phentolamine (5 mg/kg) suppressed self-stimulation in controls and treated subjects. Phenoxybenzamine (10 mg/kg) reduced the response rate for the brain reward but did not abolish the behavior in the 6-OHDA-treated animals and had minor effects in controls. Propranolol (10 mg/kg) had no effects. The 6-OHDA subjects tested for the effects of D-amphetamine and L-amphetamine (0.5 mg/kg) showed facilitation of responding after the former but not after the latter. Self-stimulation in the 6-OHDA subjects was suppressed by treatment with alpha-methyl-p-tyrosine and pimozide. The significance of these findings is discussed in terms of the use of alpha-adrenoreceptor antagonists to separate the pre- from the post-synaptic action of released norepinephrine and in terms of the norepinephrine hypothesis of rewarding effects of brain stimulation in the dorsal pons.
D000818:Animals; D000831:Animals, Newborn; D006892:Hydroxydopamines / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D012653:Self Stimulation / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine