Blockade of presynaptic voltage-gated calcium channels in the medial prefrontal cortex of neonatal rats leads to post-pubertal alterations in locomotor behavior.
Although the etiology of neurodevelopmental mental disorders remains obscure, converging lines of evidence using animal modeling suggest a critical role for activity-dependent neurodevelopmental processes during neonatal life. Here, we report the behavioral effects of a novel technique designed to induce targeted, transient disruption of activity-dependent processes in early development via reduction of calcium-mediated neurotransmitter release. We examined the post-pubertal behavioral effects of neonatal (postnatal day 7) medial prefrontal cortex infusion of either vehicle or N-type and P/Q-type presynaptic voltage-dependent calcium channel blockers (omega-conotoxins MVIIA and MVIIC respectively; 6.8 and 45 pmol infused respectively) in rat pups. In a test of amphetamine-induced behavioral sensitization, neonatal omega-conotoxin MVIIA treatment significantly increased locomotion following repeated amphetamine injections (1.5 mg/kg i.p.) and significantly decreased locomotion following repeated saline injections relative to animals treated neonatally with vehicle. However, there was no effect of conotoxin treatment on the long-term expression of amphetamine sensitization. Neonatal treatment with omega-conotoxins had no effect on the other behaviors assayed, namely, acoustic startle response, prepulse inhibition of startle, novelty- and amphetamine-induced (1.5 mg/kg i.p.) locomotion, and anxiety-like behavior in the elevated plus-maze. These data confirm that transient, region-specific disruption of synaptic transmission during early development can have long-term effects on behaviors relevant to neurodevelopmental mental disorders.
Departments of Psychiatry and Neurology and Neurosurgery, Douglas Hospital Research Centre, McGill University, 6875 LaSalle Boulevard, Verdun, Montreal, Quebec, Canada H4H 1R3.
Clifford M
CM
Cassidy
Rémi
R
Quirion
Lalit K
LK
Srivastava
D000375:Aging / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000502:physiology; D001523:Mental Disorders / Q000378:metabolism / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013995:Time; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D000697:Central Nervous System Stimulants; D020960:omega-Conotoxins; C078452:ziconotide; D000661:Amphetamine