Neuroscience
"However, we'll still take plenty of food and opioid agonists!"
Unlike mice with the dopamine D2 receptor "knocked out," D1 receptor-deficient mice will no longer self-administer cocaine:
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Neuroscience
D1 Receptor Knock-Out Mice Say, "No Cocaine for Us!"
"However, we'll still take plenty of food and opioid agonists!"
Unlike mice with the dopamine D2 receptor "knocked out," D1 receptor-deficient mice will no longer self-administer cocaine:
Caine SB, Thomsen M, Gabriel KI, Berkowitz JS, Gold LH, Koob GF, Tonegawa S, Zhang J, Xu M. (2007). Lack of Self-Administration of Cocaine in Dopamine D1 Receptor Knock-Out Mice. J. Neurosci. 27:13140-13150.
Evidence suggests a critical role for dopamine in the reinforcing effects of cocaine in rats and primates. However, self-administration has been less often studied in the mouse species, and, to date, "knock-out" of individual dopamine-related genes in mice has not been reported to reduce the reinforcing effects of cocaine. We studied the dopamine D1 receptor and cocaine self-administration in mice using a combination of gene-targeted mutation and pharmacological tools. Two cohorts with varied breeding and experimental histories were tested, and, in both cohorts, there was a significant decrease in the number of D1 receptor knock-out mice that met criteria for acquisition of cocaine self-administration (2 of 23) relative to wild-type mice (27 of 32). After extinction of responding with saline self-administration, dose–response studies showed that cocaine reliably and dose dependently maintained responding greater than saline in all wild-type mice but in none of the D1 receptor knock-out mice. The D1-like agonist SKF 82958 (2,3,4,5,-tetrahydro-6-chloro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrobromide) and the D2-like agonist quinelorane both functioned as positive reinforcers in wild-type mice but not in D1 receptor mutant mice, whereas food and intravenous injections of the opioid agonist remifentanil functioned as positive reinforcers in both genotypes. Finally, pretreatment with the D1-like antagonist SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-01] produced surmountable antagonism of the reinforcing effects of cocaine in the commonly used strain C57BL/6J. We conclude that D1 receptor knock-out mice do not reliably self-administer cocaine and that the D1 receptor is critical for the reinforcing effects of cocaine and other dopamine agonists, but not food or opioids, in mice.
- Was I Wrong?
In honor of The Neurocritic's 10th anniversary, I'd like to announce a new occasional feature: Was I Wrong? In science, as in life, we learn from our mistakes. We can't move forward if we don't admit we were wrong and revise our entrenched...
- The Joy Of 5-ht4 Receptors
Move over, melanocortin receptors, 5-HT4 receptors are ready to take your place. Agonists of the 5-HT4 receptor, a subtype of the serotonin receptor family, seem to do the following, according to recently published reports: (1) mediate the appetite-suppressing...
- The Joy Of Melanocortin Receptors
Lose Weight and Improve Your Sex Life! Those two pitches account for approximately 95% of all spam, right? But what if you could manufacture one drug that promises to do both things? Think of the profits!! Although it sounds too good to be true, there...
- Neuropsychology Abstract Of The Day: Alzheimer's Disease
Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer's disease transgenic mouse model J Neurochem. 2011 Sep; 118(5): 928-38 Authors: Fabbro S, Schaller K, Seeds NW Abstract...
- Abstract Of The Day: Assessing Neurocognitive Toxicity In Animal Models
Bertaina-Anglade V, Enjuanes E, Morillon D, & Drieu la Rochelle C. (2006). The object recognition task in rats and mice: A simple and rapid model in safety pharmacology to detect amnesic properties of a new chemical entity. J Pharmacol Toxicol Methods,...