Comparison of Cannabinoid CB1 Receptor Binding in Adolescent and Adult Rats: A Positron Emission Tomography Study Using [18F]MK-9470

Despite the important role of cannabinoid CB1 receptors (CB1R) in brain development, little is known about their status during adolescence, a critical period for both the development of psychosis and for initiation to substance abuse. In the present study, we assessed the ontogeny of CB1R in adolescent and adult rats in vivo using positron emission tomography with [18F]MK-9470. Analysis of covariance (ANCOVA) to control for body weight that would potentially influence [18F]MK-9470 values between the two groups revealed a main effect of age (F(1,109)=5.0, P = 0.02) on [18F]MK-9470 absolute binding (calculated as percentage of injected dose) with adult estimated marginal means being higher compared to adolescents amongst 11 brain regions. This finding was confirmed using in vitro autoradiography with [3H]CP55,940 (F(10,99)=140.1, P < 0.0001). This ontogenetic pattern, suggesting increase of CB1R during the transition from adolescence to adulthood, is the opposite of most other neuroreceptor systems undergoing pruning during this period

AUTORADIOGRAPHIC STUDY OF THE PROPERTIES OF THE IONOTROPIC NON-NMDA RECEPTOR OFEXCITATORY AMINO ACIDS IN AVIAN BRAIN AND IN MAMMALIAN BASAL GANGLIA AFTER LESIONING OF AFFERENT NERVE FIBERS

IN THE FIRST SECTION OF THIS STUDY, THE NON-N-METHYL-D-ASPARTATE (NON-NMDA) BINDING SITES WERE CHARACTERIZED IN CHICK BRAIN USING QUANTITATIVE AUTORADIOGRAPHY AND [3H]CNQX AS A RADIOLIGAND. [3H]CNQX BINDING SITES WERE DENSELY LOCALIZED IN THE MOLECULAR LAYER OF CEREBELLUM. ANALYSIS OF EQUILIBRIUM BINDING DATA IN THE CEREBELLAR MOLECULAR LAYER INDICATED THAT [3H}CNQX BOUND TO A SINGLE CLASS OF SITES (KD=78.9+-11.8 NM AND BMAX =41.2+-3.0 PMOL/GR PROTEIN). COMPETITION EXPERIMENTS INDICATED THAT IN THE CEREBELLAR MOLECULAR LAYER AND OPTIC LOBES, THESE SITES WERE MORE SENSITIVE TO KAINATE THAN AMPA. HOWEVER, NON--NMDA BINDING SITES IN FOREBRAIN REGIONS APPEARED TO BE DIFFERENT AND WERE EQUALLY SENSITIVE TO AMPA AND KAINATE. IN THE SECOND SECTION OF THIS STUDY, CELLULARLOCALIZATION OF EXCITATORY AMINO ACID RECEPTORS ON PRESYNAPTIC DOPAMINERGIC NERVE TERMINALS WAS INVESTIGATED AFTER UNILATERAL LESIONING OF THE MEDIAL FOREBRAIN BUNDLE (MFB) WITH 6-OHDA INJECTIONS, USING RECEPTOR AUTORADIOGRAPHY. THENON-NMDA BINDING SITES WERE CHARACTERIZED USING [3H]KAINATE AND [3H]AMPA. THE DOPAMINE UPTAKE COMPLEX WAS LOCALIZED USING [3H]GBR 12935. MFB LESIONING RESULTED IN A SIGNIFICANT DECREASE OF [3H]GBR BINDING IN CAUDATE-PUTANEN COMPLEXAND NUCLEUS ACCUMBENS IPSILATERAL TO THE LESIONED SIDE. KINETIC EXPERIMENTS PERFORMED IN CAUDATE-PUTAMEN COMPLEX AND NUCLEUS ACCUMBENS INDICATED THAT THE MAXIMUM NUMBER OF [3H]KAINATE AND [3H]AMPA BINDING SITES WERE SIGNIFICANTLY DECREASED BY 17 TO 26%. (ABSTRACT TRUNCATED)ΣΤΟ ΠΡΩΤΟ ΜΕΡΟΣ ΜΕΛΕΤΗΘΗΚΑΝ ΟΙ ΥΠΟΔΟΧΕΙΣ ΜΗ-NMDA ΣΤΟΝ ΕΓΚΕΦΑΛΟ ΤΟΥ ΩΡΙΜΟΥ ΚΟΤΟΠΟΥΛΟΥ, ΜΕ ΧΡΗΣΗ ΤΗΣ IN VITRO ΠΟΣΟΤΙΚΗΣ ΑΥΤΟΡΑΔΙΟΓΡΑΦΙΑΣ ΚΑΙ ΤΟ [3Η]CNQX ΩΣ ΣΗΜΑΣΜΕΝΟ ΔΕΣΜΕΥΤΗ. ΠΕΙΡΑΜΑΤΑ ΚΑΤΑΝΟΜΗΣ ΤΗΣ ΔΕΣΜΕΥΣΗΣ ΤΟΥ [3Η]CNQX ΕΔΕΙΞΑΝ ΤΑΥΨΗΛΟΤΕΡΑ ΕΠΙΠΕΔΑ ΔΕΣΜΕΥΣΗΣ ΣΤΗ ΜΟΡΙΑΚΗ ΣΤΙΒΑΔΑ ΤΗΣ ΠΑΡΕΓΚΕΦΑΛΙΔΑΣ. ΠΕΙΡΑΜΑΤΑ ΚΟΡΕΣΜΟΥ ΤΗΣ ΔΕΣΜΕΥΣΗΣ ΤΟΥ [3H]CNQX ΣΤΗΝ ΠΕΡΙΟΧΗ ΑΥΤΗ ΕΔΩΣΑΝ KD=78.9+-11.8NM, BMAX=41.2 PMOL/MG ΠΡΩΤΕΙΝΗΣ. ΦΑΡΜΑΚΟΛΟΓΙΚΑ ΠΕΙΡΑΜΑΤΑ ΕΔΕΙΞΑΝ ΟΤΙ ΣΤΗΝ ΠΑΡΕΓΚΕΦΑΛΙΔΑ ΚΑΙ ΣΤΟΥΣ ΟΠΤΙΚΟΥΣ ΛΟΒΟΥΣ ΟΙ ΜΗ-NMDA ΥΠΟΔΟΧΕΙΣ ΒΡΙΣΚΟΝΤΑΙ ΣΕ ΜΙΑ ΔΙΑΜΟΡΦΩΣΗ ΠΟΥ ΑΝΤΙΣΤΟΙΧΕΙ ΚΥΡΙΩΣ ΣΤΟΝ ΚΑΙΝΙΚΟ ΥΠΟΔΟΧΕΑ. ΣΕ ΠΡΟΣΘΙΕΣ ΠΕΡΙΟΧΕΣ ΟΙ ΜΗ-NMDA ΥΠΟΔΟΧΕΙΣ ΒΡΙΣΚΟΝΤΑΙ ΣΕ ΜΙΑ ΔΙΑΜΟΡΦΩΣΗ ΠΟΥ ΑΝΤΙΣΤΟΙΧΕΙ ΣΕ ΕΝΑΝ ΚΟΙΝΟ AMPA/ΚΑΙΝΙΚΟ ΥΠΟΔΟΧΕΑ. ΣΤΟ ΔΕΥΤΕΡΟ ΜΕΡΟΣ ΕΛΕΧΘΗΚΑΝ ΤΑ ΕΠΙΠΕΔΑ ΤΩΝ ΥΠΟΔΟΧΕΩΝ ΜΗ-NMDA ΠΑΝΩ ΣΤΙΣ ΤΕΛΙΚΕΣ ΑΠΟΛΗΞΕΙΣ ΤΩΝ ΝΤΟΠΑΜΙΝΕΡΓΙΚΩΝ ΙΝΩΝ ΣΤΟ ΡΑΒΔΩΤΟ ΣΩΜΑ ΜΕΤΑ ΑΠΟ ΜΟΝΟΠΛΕΥΡΗ ΒΛΑΒΗ ΤΗΣ ΔΕΞΙΑΣ ΕΣΩ ΤΗΛΕΓΚΕΦΑΛΙΚΗΣ ΔΕΣΜΙΔΑΣ (ΕΤΔ) ΤΟΥΕΓΚΕΦΑΛΟΥ ΤΟΥ ΕΠΙΜΥΟΣ, ΜΕ ΤΗΝ ΤΕΧΝΙΚΗ ΤΗΣ ΑΥΤΟΡΑΔΙΟΓΡΑΦΙΑΣ ΚΑΙ ΧΡΗΣΗ ΤΩΝ [3H]AMPA ΚΑΙ ΤΟΥ [3H]ΚΑΙΝΙΚΟΥ ΟΞΕΟΣ. Η ΒΛΑΒΗ ΤΗΣ ΕΤΔ ΤΟΥ ΕΓΚΕΦΑΛΟΥ ΤΟΥ ΕΠΙΜΥΟΣ ΟΔΗΓΗΣΕ ΣΕ ΣΗΜΑΝΤΙΚΗ ΜΕΙΩΣΗ ΤΗΣ ΔΕΣΜΕΥΣΗΣ ΤΟΥ ΣΥΜΠΛΕΓΜΑΤΟΣ ΕΠΑΝΑΠΡΟΣΛΗΨΗΣ ΤΗΣ ΝΤΟΠΑΜΙΝΗΣ (ΠΟΥ ΠΡΟΣΔΙΟΡΙΣΤΗΚΕ ΜΕ [3H]GBR) ΣΤΟΝ ΚΕΡΚΟΦΟΡΟ ΠΥΡΗΝΑ-ΚΕΛΥΦΟΣ ΚΑΙ ΣΤΟΝ ΕΠΙΚΛΙΝΗ ΠΥΡΗΝΑ, ΟΜΟΠΛΕΥΡΑ ΜΕ ΤΗ ΒΛΑΒΗ. ΠΕΙΡΑΜΑΤΑ ΚΟΡΕΣΜΟΥ ΤΗΣ ΔΕΣΜΕΥΣΗΣ ΣΤΙΣ ΠΕΡΙΟΧΕΣ ΕΔΕΙΞΑΝ ΟΤΙ ΤΟ [3Η]ΚΑΙΝΙΚΟ ΚΑΙ ΤΟ [3H]AMPA ΕΜΦΑΝΙΖΟΥΝ ΕΛΑΤΤΩΣΗ ΤΟΥΜΕΓΙΣΤΟΥ ΑΡΙΘΜΟΥ ΘΕΣΕΩΝ ΔΕΣΜΕΥΣΗΣ ΣΤΗΝ ΠΛΕΥΡΑ ΤΗΣ ΒΛΑΒΗΣ 17-26%. (ΠΕΡΙΚΟΠΗΠΕΡΙΛΗΨΗΣ)

Dopamine antagonists in the orbital prefrontal cortex reduce prepulse inhibition of the acoustic startle reflex

ZAVITSANOU, K., J. CRANNEY AND R. RICHARDSON. Dopamine antagonists in the orbital prefrontal cortex reduce prepulse inhibition of the acoustic startle reflex in the rat. PHARMACOL BIOCHEM BEHAV 63 (1) 55-61, 1999.-Schizophrenia is characterized by, among other things, (a) information processing deficits that have been indexed by a number of measures, including deficits in prepulse inhibition (PPI) of the acoustic startle reflex; and (b) pathophysiology of the frontal lobe. Recent studies have implicated the prefrontal cortex (PFC) in the modulation of PPI in rats. These studies suggest that dopamine (DA) ablation of the PFC (using 6-OHDA) leads to disruption of PPI. To better understand the role of DA type 1 (D 1 ) and type 2 (D 2 ) receptors in the modulation of PPI, we investigated the effects of two pharmacologically distinct DA antagonists on the modulation of PPI. Microinjection of SCH23390 (a D 1 antagonist) into the orbital PFC markedly decreased PPI (at 0.1, 0.5, and 1.5 g), whereas raclopride (a D 2 antagonist) decreased PPI at some doses (0.1 and 0.5 mg/ml) but not at others (5.0 g). We conclude that both D 1 and D 2 receptors mediate the cortical modulation of PPI. © 1999 Elsevier Science Inc. Dopamine antagonists Prepulse inhibition Prefrontal cortex Schizophrenia PREPULSE inhibition (PPI) of the acoustic startle reflex (ASR) occurs when a weak, nonstartle-eliciting stimulus (prepulse), presented 30-500 ms before the startle-eliciting acoustic stimulus, results in the reduction of ASR amplitud

Investigation of M1/M4 Muscarinic Receptors in the Anterior Cingulate Cortex in Schizophrenia, Bipolar Disorder, and Major Depression Disorder

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